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OBJECTIVE: To further clarify the anticancer mechanisms of Liujunzi decoction and provide possible targets for the treatment of advanced-stage nonsmall cell lung cancer (NSCLC) by re-analyzing differential gene expression profile of peripheral blood mononuclear cells (PBMCs) from Liujunzi decoctiontreated NSCLC patients receiving first-line chemotherapy. METHODS: The PBMC gene expression microarray data set GSE61926 was retrieved from a high throughput gene expression database. Differentially expressed genes (DEGs) were screened by paired sample t-test and the multiple ratio method. Gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were performed using the DAVID database. The protein-protein interaction (PPI) network was constructed using interaction gene library retrieval tools and Cytoscape software. RESULTS: A total of 162 DEGs were identified, with 67 upregulated genes and 95 downregulated genes. The functional distribution of Gene Oncology (GO) genes showed that DEGs were mostly concentrated in extracellular regions, calcium ion binding, and transcriptase activity. KEGG pathway analysis showed that cytokine-cytokine receptor interactions were significantly enriched. PPI network analysis screened out the top 10 central protein-coding genes with the highest nodal degree: IL2, PIWIL4, DICER1, PIWIL2, SAA1, XCL1, IL22RA1, ARHGAP11A, DCP1A, and GDNF. Among them, the central protein-coding gene with the highest node degree was IL2. In addition, the central protein-coding genes with high node degrees and high molecular complex detection (MCODE) scores were PIWIL4, DICER1, PIWIL2, and DCP1A, all of which are related to tumor development. CONCLUSIONS: One signaling pathway and 10 central protein-coding genes related to anticancer mechanisms were screened by re-analysis of GSE61926 data. IL2, PIWIL4, DICER1, PIWIL2, and DCP1A may have important roles in the mechanism of Liujunzi decoction treatment against NSCLC. Our results suggest that the anticancer mechanism of Liujunzi decoction may be related to gene silencing by RNA and the biological processes of piwi-interacting RNA and other small RNAs.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Biologia Computacional/métodos , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Medicamentos de Ervas Chinesas , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Interleucina-2/genética , Leucócitos Mononucleares/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Ribonuclease III/genética , Ribonuclease III/metabolismoRESUMO
Feiyanning formula (FYN) is a traditional Chinese medicine (TCM) prescription used for more than 20 years in the treatment of lung cancer. FYN is composed of Astragalus membranaceus, Polygonatum sibiricum, Atractylodes macrocephala, Cornus officinalis, Paris polyphylla, and Polistes olivaceous, etc. All of them have been proved to have anti-tumor effect. In this study, we used the TCM network pharmacological analysis to perform the collection of compound and disease target, the prediction of compound target and biological signal and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. It was found that the activation of mitochondrial pathway might be the molecular mechanism of the anti-lung cancer effect of FYN. The experimental results showed that FYN had an inhibitory effect on the growth of lung cancer cells in a dose-dependent and time-dependent manner. Moreover, FYN induced G2/M cell cycle arrest and apoptotic cell death as early as 6 h after treatment. In addition, FYN significantly induced mitochondrial membrane depolarization and increased calreticulin expression. Metabolomics analysis showed the increase of ATP utilization (assessed by a significant increase of the AMP/ATP and ADP/ATP ratio, necessary for apoptosis induction) and decrease of polyamines (that reflects growth potential). Taken together, our study suggested that FYN induced apoptosis of lung adenocarcinoma cells by promoting metabolism and changing the mitochondrial membrane potential, further supporting the validity of network pharmacological prediction.
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Although osimertinib, an EGFR tyrosine kinase inhibitor, has become the standard therapy for treating non-small cell lung cancer (NSCLC) patients with EGFR-activating mutation, upregulation of MCL-1 induces acquired resistance to osimertinib. Bufalin, a natural digoxin-like ingredient isolated from a traditional Chinese medicine Chan Su, has been shown to downregulate MCL-1 in NSCLC cells. However, whether bufalin reverses this acquired resistance to osimertinib in NSCLC cells remains unclear. In this study, bufalin reduced cell viability and promoted apoptosis in osimertinib-resistant cells. Moreover, co-treatment with bufalin and osimertinib restored the sensitivity of osimertinib-resistant cells to osimertinib-induced growth regression and apoptosis in vitro and in vivo. Mechanistically, MEK/ERK-dependent MCL-1 phosphorylation and Ku70-mediated MCL-1 overexpression confer osimertinib resistance in EGFR-mutant NSCLC cells. In osimertinib-resistant cells, bufalin modulates Ku70-mediated MCL-1 degradation, but not MEK/ERK/MCL-1 signaling. In conclusion, our study suggests that bufalin eliminates resistance to osimertinib by inhibiting Ku70-mediated MCL-1 overexpression, indicating that a combination of osimertinib and bufalin could be an effective additional treatment to overcome acquired resistance to osimertinib in NSCLC cells.
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Acrilamidas/uso terapêutico , Compostos de Anilina/uso terapêutico , Antineoplásicos/uso terapêutico , Bufanolídeos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Genes erbB-1/genética , Neoplasias Pulmonares/tratamento farmacológico , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Animais , Bufanolídeos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Imunofluorescência , Marcação In Situ das Extremidades Cortadas , Neoplasias Pulmonares/genética , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de NeoplasiasRESUMO
Traditional Chinese medicine (TCM) is an important part of the treatment of primary liver cancer (PLC) in China; however, the current instructions for the integrative use of traditional Chinese and Western medicine for PLC are mostly based on expert opinion. There is no evidence-based guideline for clinical practice in this field. Therefore, the Shanghai Association of Chinese Integrative Medicine has established a multidisciplinary working group to develop this guideline, which focuses on the most important questions about the use of TCM during PLC treatment. This guideline was developed following the methodological process recommended by the World Health Organization Handbook for Guideline Development. Two rounds of questionnaire survey were performed to identify clinical questions; published evidence was searched; the Grading of Recommendations Assessment, Development and Evaluation approach was used to evaluate the body of evidence; and recommendations were formulated by combining the quality of evidence, patient preferences and values, and other risk factors. The guideline was written based on the Reporting Items for Practice Guidelines in Healthcare tool. This guideline contains 10 recommendations related to 8 questions, including recommendations for early treatment by TCM after surgery, TCM combined with transcatheter arterial chemoembolization for advanced PLC, TCM drugs for external use, and acupuncture and moxibustion therapy.
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Medicina Integrativa/normas , Neoplasias Hepáticas/terapia , Medicina Tradicional Chinesa/normas , Terapia por Acupuntura , Venenos de Anfíbios/uso terapêutico , China , Terapia Combinada/normas , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Estadiamento de Neoplasias , Guias de Prática Clínica como AssuntoRESUMO
OBJECTIVE: To study the efficacy and safety of Shuanghuang Shengbai Granule (, SSG), a traditional Chinese herbal medicine, on myelosuppression of cancer patients caused by chemotherapy. METHODS: A total of 330 patients were randomly assigned to the treatment group (220 cases, analysed 209 cases) and the control group (110 cases, analysed 102 cases) with a 2:1 ratio by envelope method. The patients in the treatment group at the first day of chemotherapy started to take SSG for 14 days, while the patients in the control group took Leucogon Tablets. The changes of the blood routine, clinical symptoms and immune function in both groups were observed for safety and efficacy evaluation. RESULTS: At the 7th day of chemotherapy, the white blood cells (WBCs) level in the treatment group was significantly higher than that in the control group (P<0.05). After treatment, the WBCs rate in the normal range accounted for 50.2% in the treatment group, the myelosuppression of WBCs and neutrophil were mainly grade I, while 8.1% and 5.7% of patients emerged grade III and grade IV myelosuppression, respectively. The incidence of myelosuppression of the treatment group was significantly lower than that of the control group (P<0.05). The total effective rate of Chinese medicine syndrome in the treatment group was significantly higher than that in the control group (84.2% vs. 72.5%, P<0.05). The immune cell levels in both groups were maintained in the normal range. Compared with that before treatment, the levels of CD3+ and CD4+ cells were significantly increased in the treatment group after treatment (P<0.05). The discrepancy of CD3+ and CD4+ cell activity before and after treatment in both groups were significantly different (P<0.05). No obvious adverse event occurred in both groups. CONCLUSION: SSG had a protection effect on bone marrow suppression, and alleviated the clinical symptoms together with clinical safety.
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Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Células Precursoras de Granulócitos/efeitos dos fármacos , Tolerância Imunológica/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Pancitopenia/prevenção & controle , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Humanos , Masculino , Medicina Tradicional Chinesa , Pessoa de Meia-Idade , Pancitopenia/induzido quimicamente , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the relationship between inflammatory factors and two Chinese medicine (CM) syndrome types of qi stagnation and blood stasis (QSBS) and qi deficiency and blood stasis (QDBS) in patients with acute coronary syndrome (ACS). METHODS: Sixty subjects with ACS, whose pathogenesis changes belongs to qi disturbance blood stasis syndrome, were divided into 2 groups: 30 in the QSBS group and 30 in the QDBS group. The comparative analysis on them was carried out through comparing general information, coronary angiography and inflammatory factors including intracellular adhesion molecule-1 (ICAM-1), chitinase-3-like protein 1 (YKL-40) and lipoprotein-associated phospholipase A2 (Lp-PLA2). RESULTS: Compared with the QSBS group, Lp-PLA2 and YKL-40 levels in the QDBS group showed no-significant difference (P>0.05); ICAM-1 was significantly higher in the QDBS group than in the QSBS group in the pathological processes of qi disturbance and blood stasis syndrome of ACS (P<0.05). CONCLUSIONS: Inflammatory factor ICAM-1 may be an objective basis for syndrome typing of QSBS and QDBS, which provides a research direction for standardization research of CM syndrome types.
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Síndrome Coronariana Aguda/sangue , Inflamação/sangue , Síndrome Coronariana Aguda/diagnóstico por imagem , Angiografia Coronária , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , SíndromeRESUMO
Objective To observe the regulation of Shuanghuang Shengbai Granule (SHSBG) on regulating Wnt signaling pathway in tumor-bearing mice with chemotherapy induced myelosuppression. Methods Chemotherapy induced myelosuppression model was established in Lewis lung tumor bearing mice by intraperitoneal injection of cyclophosphamide (CTX). And then they were intervened by SHSBG. Routine white blood cell (WBC) count, red blood cell (RBC) count, platelet count, and tumor mass were calculated. Ratios of bone marrow hematopoietic stem cell (Sca, CD34 double positive cells) were detec- ted by flow cytometry. mRNA expression of main genes in Wnt signaling pathway (Wnt, ß-catenin, Frizzted, DSH, GSK3) were detected using real time fluorescent quantitative PCR. Results The number of WBC and ratio of hematopoietic stem cells in the treatment group were higher than those in the model group (P<0. 05). Expressions of Wnt, ß-catenin, Frizzted, DSH, and GSK3 mRNA in the bone marrow were higher in the treatment group than in the model group (P <0. 05). Expressions of Wnt, ß-catenin, Frizzted, and DSH mRNA expression in tumors were lower in the treatment group than in the model group (P <0. 05). There was no statistical difference in counts of RBC and platelet, tumor mass, or GSK3 mR- NA expression among all groups (P >0. 05). Conclusions The mechanism for SHSBG treating myelo-suppression was related to regulating Wnt signaling pathway. Besides, it had dual regulation effect on Wnt signaling pathway, up-regulating expressions of main genes in Wnt signaling pathway while inhibiting ex- pressions of partial genes in tumors.
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Antineoplásicos , Medicamentos de Ervas Chinesas , Doenças Hematológicas , Via de Sinalização Wnt , Animais , Antineoplásicos/efeitos adversos , Ciclofosfamida , Medicamentos de Ervas Chinesas/farmacologia , Quinase 3 da Glicogênio Sintase/metabolismo , Doenças Hematológicas/induzido quimicamente , Camundongos , Via de Sinalização Wnt/efeitos dos fármacos , beta CateninaRESUMO
OBJECTIVE: To observe the effect of bufalin combined Gefitinib on lung cancer H1975 cells, and to explore its potential mechanisms for anti-tumor. METHODS: The cytostatic effects of bufalin (1 -100 nmol/L), gefitinib (0.1-20 micromol/L), and bufalin plus gefitinib on H1975 cells were evaluated by MTT assay. Their effects on apoptosis of H1975 cells were determined by flow cytometry (FCM). Their effects on expressions of epidermal growth factor receptor (EGFR) and Met signal pathway related proteins in H1975 cells were detected by Western blot. RESULTS: Results of MTT assay showed that gefitinib over 5 micromol/L could inhibit H1975 cells. But combined therapy of bufalin and gefitinib could potently inhibit the growth of H1975 cells. Results of FCM showed the apoptotic rate was 61.64% +/- 5.61% in the bufalin plus gefitinib group, obviously higher than that of the bufalin group (18.34% +/- 3.42%) and the gefitinib group (7.32% +/- 1.08%), showing statistical difference (P < 0.01). Results of Western blot showed the protein expressions of p-EGFR, p-Met, p-Akt, and p-mTOR in H1975 cells could be markedly down-regulated by bufalin plus gefitinib. CONCLUSIONS: Combination of bufalin and gefitinib potently inhibited the growth of H1975 cells, and induced cell apoptosis. The potential mechanism for anti-tumor might be involved in blocking EGFR-PI3k/Akt pathway.
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Bufanolídeos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Quinazolinas/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Receptores ErbB/metabolismo , Gefitinibe , Humanos , Neoplasias Pulmonares/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, have shown promising therapeutic efficacy in nonsmall cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor- (EGFR-) activating mutation. However, the inevitable recurrence resulting from acquired resistance has limited the clinical improvement in therapy outcomes. Many studies demonstrate that hepatocyte growth factor- (HGF-) Met axis plays an important role in tumor progression and drug sensitivity. HGF may induce resistance to EGFR-TKIs in EGFR mutant lung cancer cells by Met/PI3K/Akt signaling. The purpose of this study was to determine whether bufalin, a major bioactive component of Venenum Bufonis, could reverse HGF-induced resistance to reversible and irreversible EGFR-TKIs in mutant lung cancer cells PC-9, HCC827, and H1975. Our studies showed that bufalin could reverse resistance to reversible and irreversible EGFR-TKIs induced by exogenous HGF in EGFR mutant lung cancer cells by inhibiting the Met/PI3K/Akt pathway and inducing death signaling. These results suggested that bufalin might have a potential to overcome HGF-induced resistance to molecular-targeted drugs for lung cancer.
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OBJECTIVE: Malignant tumor cells were found with an abnormal cell cycle. Previous in vivo experiment had confirmed the Feiyanning's intervention effect on checkpoint signaling of G1/S in the cell cycle. This study was to further observe the expressions of nucleosome conformation-regulating factors intervened by Feiyanning decoction in S phase. METHODS: Lewis lung carcinoma models of C57BL/6 mice were established. Sixty mice were randomly divided into four groups: normal control group, model control group, Feiyanning group, and cisplatin group. There were 15 mice in each group. Tumor weight and tumor inhibition rate were observed. In addition, the cell cycle distribution was detected by flow cytometry and the proliferation index was calculated. Furthermore, mRNA and protein expressions of H3-K56, regulator of Ty1 transposition 109 (Rtt109), antisilencing function 1 (Asf1) and E2F1 were analyzed by real-time polymerase chain reaction and Western blot methods, respectively. RESULTS: The tumor weights of mice in the Feiyanning group and the cisplatin group were lower than those in the model group (P<0.01), with tumor inhibition rates of 27.92% and 42.50%, respectively. Cancer cell proliferation index and proportion of cancer cell population in S phase in the Feiyanning group were significantly lower than those in the cisplatin group (P<0.01). The mRNA and protein levels of H3-K56, Rtt109, Asf1, E2F1 in the Feiyanning group were lower than those in the model group (P<0.05). CONCLUSION: Feiyanning plays a role in intervening in the abnormal cell cycle by nucleosome conformation-regulating factors and thus inhibits the lung cancer cell proliferation.
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Carcinoma Pulmonar de Lewis/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Pulmonares/metabolismo , Nucleossomos , Animais , Carcinoma Pulmonar de Lewis/patologia , Ciclo Celular/efeitos dos fármacos , Divisão Celular , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de SinaisRESUMO
BACKGROUND: Tumor markers are widely used in clinical practice and have become important indicators in assessing cancer progress. There is increasing concern that chemotherapy combined with traditional Chinese medicine has effects in decreasing the level of tumor markers. OBJECTIVE: To investigate the effects of chemotherapy combined with Kangliu Zengxiao Decoction (KLZX), a compound Chinese herbal drug, on tumor markers carbohydrate antigen 50 (CA 50), cytokeratin 19 fragment (CYFRA21-1) and carcinoembryonic antigen (CEA) in patients with advanced non-small-cell lung cancer (NSCLC) and to explore the relationships between clinical efficacy and tumor markers. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Patients were included from Punan Hospital of Shanghai Pudong New District and Longhua Hospital between October 2008 and December 2009. Seventy-four subjects with advanced NSCLC were randomly assigned into treatment group (n=37) and control group (n=37). Patients in the control group were treated with chemotherapy alone while patients in the treatment group were treated with chemotherapy combined with KLZX. Chemotherapy of NP (vinorelbine + cisplatin) was given for two cycles and patients in the treatment group were administered with KLZX during chemotherapy. MAIN OUTCOME MEASURES: Levels of CA50, CYFRA21-1 and CEA before and after treatment were evaluated and the relationship between changes in levels of tumor makers and tumor size, clinical symptoms and living condition score (Karnofsky score) was analyzed. RESULTS: No patients achieved a complete remission. The disease control rates (complete remission (CR)+partial remission (PR)+no change (NC)) were 89.20% (33/37) and 70.30% (26/37) in the treatment and control group respectively (P<0.05). The levels of CA50, CYFRA21-1 and CEA were clearly decreased in the treatment group after treatment (P<0.05) while also decreased in the patients without progression of disease. There were no obvious changes of CA50, CYFRA21-1 and CEA in the control group, and there was even a trend of increase. Furthermore, the improvement rates of clinical syndrome were 51% (19/37) vs 11% (4/37) (P<0.05) in the treatment group and control group respectively. The total response rates of quality of life were 91.89% (34/37) vs 56.76% (21/37) (P<0.01) in the treatment and control group respectively. CONCLUSION: Combined chemotherapy with KLZX in treating advanced NSCLC can acquire better stabilizing tumor foci, decrease levels of tumor markers and improve the clinical symptoms and Karnofsky score.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Fitoterapia , Adolescente , Adulto , Idoso , Antígenos de Neoplasias/análise , Antígenos Glicosídicos Associados a Tumores/análise , Biomarcadores Tumorais/metabolismo , Antígeno Carcinoembrionário/análise , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/uso terapêutico , Feminino , Humanos , Queratina-19/análise , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Vimblastina/análogos & derivados , Vimblastina/uso terapêutico , Vinorelbina , Adulto JovemRESUMO
OBJECTIVE: To describe the characteristic of tongue images of patients with lung cancer of different Chinese medicine (CM) syndromes and to reveal the elemental rule on the changes of the tongue images. METHODS: A total of 207 patients with lung cancer were divided into four syndrome groups according to the theory of CM: Fei and Shen deficiency syndrome (Group A, 72 cases), Pi deficiency and phlegm deficiency and phlegm) and Shen (deficiency and phlegm) deficiency syndrome (Group A, 72 cases), Pi (deficiency and phlegm) deficiency and phlegm dampness syndrome (Group B, 57 cases), phlegm-heat retention in Fei (Group C, 36 cases) and yin asthenia generating intrinsic heat syndrome (Group D, 42 cases). The tongue parameters were detected by tongue image digital analysis instrument, and the tongue images were described with qualitative, tongue color and quantitative analysis, respectively. The International Commission on Illumination (CIE) L·a·b (CIELAB) color model was used for the quantitative classification. RESULTS: There was a significant statistical difference between different syndrome groups of lung cancer on tongue color, coating color, and thickness of tongue coating (P<0.01), and there was significant statistical difference between the four syndrome groups on Lab values of the tongue and coating (P<0.05). The correct identification rate of discriminant function on the raw data was 65.7%, including 72.2% for Group C, 69.4% for Group A, 69.0% for Group D and 54.4% for Group B. CONCLUSIONS: A tongue image digital analysis instrument can objectively describe the tongue features of patients with different syndromes of lung cancer. The tongue diagnosis is very important to syndrome differentiation in CM. Tongue diagnosis should be combined with some important characteristics of syndromes in the future to establish a "combination of four examination methods, including inspection, auscultation, interrogation, and pulse-feeling and palpation" in the tongue diagnostic system.
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Neoplasias Pulmonares/patologia , Medicina Tradicional Chinesa , Língua , Cor , Análise Discriminante , HumanosRESUMO
PURPOSE: To observe the effect of Chinese herbal medicine by stages combined with chemotherapy in treating patients with non-small-cell lung cancer (NSCLC) of stage III or IV. METHODS: Adopting prospective, randomized, controlled, multi-centered trial design, 121 patients enrolled were assigned to the treatment group (n = 65) and the control group (n = 56). All the patients were randomized to receive chemotherapy alone or chemotherapy and Chinese herbal medicine combined (Kangliuzengxiao decoction during chemotherapy and Feiyanning decoction after chemotherapy). The main outcome measures were survival time, Karnofsky score, main clinical symptoms, and adverse reactions. RESULTS: Five patients discontinued from the trial due to oral administration of Iressa after disease progression or other reasons, and 116 patients were evaluable for clinical efficacy with 63 in the treatment group and 53 in the control group. The overall response rate were 15.87% vs. 7.55% (P = 0.170), and the disease control rate were 85.71% vs. 71.70% in the treatment and control group (P = 0.063), respectively. The median survival time was 16.17 months vs. 12.00 months in the treatment and control group (P = 0.165), respectively. In addition, adverse reactions such as leucopenia in the treatment group were less than those in the control group (P = 0.039). CONCLUSIONS: Chinese herbal medicine combined with chemotherapy showed favorable effect in improving quality of life and prolonging survival time on patients with advanced NSCLC.
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Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Adenocarcinoma/patologia , Adolescente , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Cisplatino/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Taxa de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vinorelbina , Adulto JovemRESUMO
OBJECTIVE: To observe the effect of Kangliu Zengxiao Decoction (KLZX) in treating patients with advanced non-small cell lung cancer (NSCLC). METHODS: Sixty-one patients with confirmed diagnosis of NSCLC of IIIa-IV stage were randomly assigned to the treatment group (32 patients) and the control group (29 patients). Both groups were treated with two cycles of chemotherapy NP regimen, while KLZX was given to the treatment group additionally. RESULTS: As compared with the control group, the improvements in the treatment group was better in terms of majority of clinical symptoms, median survival time, Karnofski score and body weight, also in increasing immune function, decreasing levels of tumor marks (CEA, VEGF, CYFRA21-1) and alleviating hemopoietic and digestive adverse reactions. But the two groups showed insignificant difference in reducing tumor size and stabilizing tumor foci. CONCLUSION: Combined use of KLZX and chemotherapy has the toxicity reducing and effect enhancing action, is one of the effective approaches for treatment of advanced NSCLC.
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Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Fitoterapia , Adulto , Idoso , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Método Simples-Cego , Resultado do TratamentoRESUMO
Physical constitution theory is an important part of traditional Chinese medicine theory. Physical constitution is associated with the incidence, development and prognosis of diseases. Gene polymorphism is a result of the interaction between internal and external environments during the human evolution, and it is the reason for differences in biological characteristics and disease susceptibility of individuals. Current status of the research on physical constitution theory, lung cancer syndromes and gene polymorphism are summarized in this paper. Exploring lung cancer syndromes from the point of view of gene polymorphism may reveal the scientific connotation of lung cancer syndromes, and provide new evidence and method for diagnosis of lung cancer.
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Adenocarcinoma/genética , Constituição Corporal , Neoplasias Pulmonares/genética , Polimorfismo Genético , Adenocarcinoma/diagnóstico , Adenocarcinoma/etiologia , Adenocarcinoma de Pulmão , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/etiologia , Medicina Tradicional ChinesaRESUMO
OBJECTIVE: To study the effects of Feiyanning Decoction, a compound traditional Chinese herbal medicine, on proliferation of lung adenocarcinoma cell line A549 cells and their production of interleukin-6 (IL-6) and IL-8 induced by tumor necrosis factor-alpha (TNF-alpha). METHODS: A549 cells were incubated with rat serum containing Feiyanning Decoction at 15% for 24, 48 and 72 h respectively. The cell proliferation was examined by 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2, 4-disulfophenyl)-2H-tetrazolium, monosodium salt assay (WST-8). The production of IL-6 and IL-8 was tested by enzyme-linked immunosorbent assay after 48-hour treatment of reagents, and the expressions of IL-6 and IL-8 mRNAs were detected by reverse transcription-polymerase chain reaction. RESULTS: Serum containing Feiyanning Decoction had obvious inhibitive functions in A549 cell proliferation after 48- and 72-treatment. TNF-alpha (1 microg/L) strongly induced the production of IL-6 and IL-8 as compared with the control serum in A549 cells, and the induced cytokine production was significantly suppressed by 15% serum containing Feiyanning Decoction (P<0.01). In addition, serum containing Feiyanning Decoction could inhibit the mRNA expressions of IL-6 and IL-8 (P<0.01). CONCLUSION: Feiyanning Decoction can inhibit IL-6 and IL-8 production induced by TNF-alpha. It is therefore expected to be a new strategy for treating lung cancer.
Assuntos
Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Neoplasias Pulmonares/patologia , Fator de Necrose Tumoral alfa/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Animais , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Humanos , Interleucina-6/genética , Interleucina-8/genética , Neoplasias Pulmonares/metabolismo , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , SoroRESUMO
OBJECTIVE: To explore the dual regulatory effects of Shuanghuang Shengbai Granule, a compound traditional Chinese herbal medicine, on cell cycle in Lewis-bearing mice with chemotherapy-induced myelosuppression. METHODS: Thrity Lewis-bearing mice were randomly divided into control group, untreated group and treated group. A model of myelosuppression was established by peritoneal injection of cyclophosphamide to Lewis-bearing mice. Mice in the treated group were treated with Shuanghaung Shengbai Granule for 6 days. Cell cycle progressions of cells collected from bone marrow and tumor tissues were assayed by flow cytometry, and proliferation index (PI) was also calculated. Expressions of cyclin-dependent kinase 4 (CDK4), cyclin-dependent kinase 6 (CDK6) and cyclin D1 in bone marrow and tumor tissues were detected by Western blotting and immunohistochemical method. RESULTS: Percentages of bone marrow and tumor cells in G0/G1 phase in the untreated group were lower than those in the control group; however, the PI of untreated group was higher than that of the control group. The expressions of CDK4, CDK6 and cyclin D1 in bone marrow and tumor tissues in the untreated group were increased as compared with the control group. Compared with the untreated group and the control group, the percentage of bone marrow cells in G0/G1 phase was decreased, and the PI of bone marrow cells and the expressions of CDK4, CDK6 and cyclin D1 were increased in bone marrow in the treated group. However, the percentage of tumor cells in G0/G1 phase in the treated group was increased, and the PI of tumor cells and the expressions of CDK4, CDK6 and cyclin D1 in tumor tissues were decreased as compared with the untreated and control groups. CONCLUSION: Shuanghuang Shengbai Granule may have a function of cell cycle dual regulation in Lewis-bearing mice with chemotherapy-induced myelosuppression by regulating the expressions of CDK4, CDK6 and cyclin D1 in bone marrow and tumor tissues.
Assuntos
Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Ciclo Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Leucopenia/tratamento farmacológico , Animais , Células da Medula Óssea/patologia , Carcinoma Pulmonar de Lewis/complicações , Carcinoma Pulmonar de Lewis/patologia , Ciclina D1/metabolismo , Quinase 4 Dependente de Ciclina/metabolismo , Ciclofosfamida/efeitos adversos , Leucopenia/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fitoterapia , Distribuição AleatóriaRESUMO
OBJECTIVE: To study the effects of Feiyanning Decoction, a compound traditional Chinese herbal medicine, on gene expression of nuclear factor-kappaB (NF-kappaB) activated by tumor necrosis factor-alpha (TNF-alpha) in lung adenocarcinoma cell line (A549). METHODS: A549 cells were incubated with rat serum containing Feiyanning at different concentrations for 24 and 48 h, respectively. Morphology of cells was observed by an inverted microscope after treatment with reagents. The cell proliferation was examined by 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt (WST-8) assay. The expressions of NF-kappaB and inhibitor kappaBalpha (IkappaBalpha) were studied by Western blotting. NF-kappaB-dependent luciferase reporter (3 x kappaB-luc) was transfected for 24 h, and the cells were treated with the reagents for 24 h, and then the transcriptional activity of NF-kappaB promoter was detected by luciferase assay. RESULTS: TNF-alpha (1 microg/L) strongly induced the expression of NF-kappaB by approximately 1.76-fold compared with the control in the nuclei of A549 cells, and the induced NF-kappaB expression was significantly suppressed by addition of Feiyanning (P < 0.01). In addition, Feiyanning inhibited the transcriptional activity of the NF-kappaB promoter. However, we observed no significant changes in IkappaBalpha expression (P > 0.05). CONCLUSION: Feiyanning Decoction can markedly inhibit human lung cancer A549 cell proliferation, which may be partly due to inhibition of NF-kappaB activation induced by TNF-alpha. It is therefore expected to be a new strategy for treating lung cancer.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Pulmonares/genética , NF-kappa B/genética , Animais , Linhagem Celular Tumoral , Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , NF-kappa B/metabolismo , Ratos , Fator de Necrose Tumoral alfa/efeitos adversosRESUMO
OBJECTIVE: To observe the inhibitory effects of Feiyanning Decoction, a compound traditional Chinese herbal medicine for replenishing qi, nourishing essence, and diminishing stagnation by detoxification, on proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were isolated from the new-born umbilical core of human. Serum containing Feiyanning was prepared in SD rats by oral gavage of the Feiyanning Decoction for three days. The inhibitory effects of different contents of serum containing Feiyanning on the proliferation of HUVECs, human lung adenocarcinoma cell A549, and HUVECs cultured with A549-conditioned media were observed by sulforhodamine B (SRB) method; the effects on migration of HUVECs were inspected by using Boyden Chamber Transwell method, and the effects on tube formation of HUVECs were evaluated by cavity forming experiment. RESULTS: Serum containing Feiyanning at a concentration of 25%, 37.5% or 50% inhibited the proliferation of both the HUVECs and the HUVECs cultured with A549-conditioned media (P < 0.01, P < 0.05). High concentration serum containing Feiyanning inhibited the proliferation of A549 cells. Sera containing Feiyanning at concentrations of 12.5% to 37.5% inhibited the migration of HUVECs induced by 20% fetal bovine serum (P < 0.01, P < 0.05) and the formation of the primary tube of HUVECs. CONCLUSION: Feiyanning Decoction can inhibit the angiogenesis of HUVECs, which may be one of its mechanisms in inhibiting the invasion metastases of lung cancer.
Assuntos
Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Meios de Cultivo Condicionados , Células Endoteliais da Veia Umbilical Humana/citologia , Humanos , Ratos , Ratos Sprague-Dawley , SoroRESUMO
OBJECTIVE: To observe the effects of Feiyanning (FYN) formula, a compound traditional Chinese herbal medicine, on the expressions of CXCL12 and CXC chemokine receptor 4 (CXCR4) mRNAs and proteins in Lewis tumors in C57 mice. METHODS: A total of 24 C57BL-6 mice were used in this study. Lewis cells were subcutaneously injected to the right armpit to establish the tumor-bearing model. The C57 mice bearing Lewis tumor were randomly divided into untreated group, chemotherapy group, FYN group and chemotherapy plus FYN group. Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry were employed to measure the expressions of CXCL12 and CXCR4 mRNAs and proteins in Lewis tumors in C57 mice respectively. RESULTS: The rates of lung cancer metastasis in the FYN group and the chemotherapy plus FYN group were markedly lower than that in the untreated group or the chemotherapy group. The expressions of CXCL12 and CXCR4 mRNAs and proteins appeared in tumor tissue in the untreated group. Although there was no significant difference in the expressions of mRNA and protein of CXCL12 among all groups (P>0.05), the expressions of mRNA and protein of CXCR4 in the untreated group and the chemotherapy group were markedly lower than those in the FYN group and the chemotherapy plus FYN group (P<0.05). CONCLUSION: FYN can inhibit the metastasis of Lewis tumor loaded in C57 mice. Its mechanisms may be related to its down-regulation of the expression of chemokine receptor CXCR4, and affecting the role of CXCL12-CXCR4 biological axis.