RESUMEN
Five new glycosides, namely methyl 3-methoxybenzoate-4,5-di-O-ß-D-glucopyranoside (1), (1aS,3aS,3R)-3-(4'-O-ß-D-glucopyranosyl-3'-methoxyphenyl)-5,6-dioxa-bicyclo[3.3.0]octane-1-one (2), quinolin-4(1H)-one-3-O-ß-D-glucopyranoside (3), 3-methoxy-propiophenone 4-O-(6'-ß-D-xylopyranosyl)-ß-D-glucopyranoside (4), methyl 3-methoxybenzoate 4-O-(6'-ß-D-xylopyranosyl)-ß-D-glucopyranoside (5), and one known compound, bambulignan B (6) were isolated from the culms of Phyllostachys nigra var. henonis. Their structures were determined using spectroscopic analysis. All compounds were evaluated for their DPPH radical scavenging activity. Compound 6 exhibited antioxidant activity with IC50 value of 59.5 µM (positive control, L-ascorbic acid, IC50 = 12.4 µM; 2,6-ditertbutyl-4-methyl phenol, IC50 = 11.8 µM).
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CONTEXT: Leonurine hydrochloride (LH), a major alkaloid compound extracted from Leonurus japonicas Houtt. (Labiatae), is considered to have antitumor roles. OBJECTIVE: This study investigated its effects on human non-small cell lung cancer (NSCLC) H292 cells and illustrated the possible mechanism involved. MATERIALS AND METHODS: After treatment with different concentrations of LH (0, 10, 25, and 50 µmol/L) for 6, 12, 24, 48, and 72 h, the cell viability was assessed by the MTT assay. After exposed to different doses of LH for 24 h, cell-cycle distribution, cell apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) were monitored by flow cytometry. RT-PCR and western blot were used to detect the expression of apoptosis-related genes. RESULTS: LH significantly inhibited the proliferation of H292 cells in a time- and dose-dependent manner, and induced G0/G1 cell-cycle arrest. Coincidentally, LH treatment at a dose of 10, 25, and 50 µmol/L for 24 h increased apoptotic ratio from 4.9 ± 0.43% to 11.5 ± 1.12%, 19.3 ± 1.16%, and 61.3 ± 6.69%, respectively. The inhibition effect of LH on H292 cells was associated with the loss of MMP and the generation of ROS. The phosphorylation level of p38 was increased and Akt phosphorylation was reduced by LH treatment. Furthermore, LH treatment increased the expression levels of caspase-3, caspase-9 and Bax/Bcl-2. CONCLUSIONS: LH inhibits the proliferation and induces the apoptosis of H292 cells in a mitochondria-dependent pathway, and the specific mechanism need to be further explored.
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Apoptosis/efectos de los fármacos , Ácido Gálico/análogos & derivados , Lamiaceae , Neoplasias Pulmonares , Mitocondrias/efectos de los fármacos , Apoptosis/fisiología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/fisiología , Relación Dosis-Respuesta a Droga , Ácido Gálico/aislamiento & purificación , Ácido Gálico/farmacología , Ácido Gálico/uso terapéutico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Mitocondrias/fisiología , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéuticoRESUMEN
Three new phenylpropanoids, namely (7'R,8'R) guaiacylglycerol 4'-O-ß-D-[6â³-O-(4-O-ß-D-glucopyranosyl)-p-hydroxyl-benzoyl]-glucopyranoside (1), (7 R,8R) guaiacylglycerol 8-O-1'-(2',6'-dimethoxy-4'-O-ß-D-glucopyranosyl)-benzene (2), (7'R,8'R) guaiacylglycerol 4'-O-ß-D-[6â³-O-3,5-dimethoxy-4-hydroxylbenzoyl]-gluco-pyranoside (3), along with one known phenylpropanoid (4) were isolated from the ethanol extract of Phyllostachys nigra var. henonis fresh culm. The structures of all compounds were determined by analysis of UV, 1D NMR, 2D NMR, HR-ESI-MS and CD data. All compounds were evaluated for their DPPH radical scavenging activity. Compound 2 (IC50 54.9 µM) and 3 (IC50 77.2 µM) exhibited moderate antioxidant activity compared with two positive control compounds L-ascorbic acid (IC50 15.5 µM) and 2,6-ditertbutyl-4-methyl phenol (IC50 19.1 µM).
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OBJECTIVE: To explore the effects of EGFR-TKI AG1478 on the expression of FoxMl and FOXO3a genes in non-small cell cancer (NSCLC) cell lines, and explore the effect on cell proliferation and drug sensitivity to AG1478 after down-regulation of FOXMl and FOXO3a expression by RNAi technique. METHODS: Human lung cancer cells were treated with AG1478 at different concentrations. RT-PCR and Western blot were used to examine the expression of P-EGFR, FOXM1, FOXO3a mRNA and protein. After transient transfection of FOXM1 and FOXO3a siRNA, RT-PCR and Western blot were employed to determine the transfection efficiency and expression of the related proteins. CCK-8 assay, colony formation assay and flow cytometry were performed to evaluate the cell proliferation, colony formation ability and the changes in cell cycle distribution. RESULTS: The expressions of FOXM1 mRNA and protein were inhibited by AG1478 in a dose-dependent manner (both P < 0.05). After transfection with FOXM1 siRNA, the expressions of FOXM1 mRNA and protein, and proteins of cyclin B1, c-Myc, and Bcl-2 were significantly down-regulated, and the expressions of p21 and cleaved-PARP proteins were significantly up-regulated (all P < 0.05). The colony number of FOXM1siRNA transfection group was 37.3 ± 8.6, significantly lower than that of the blank control (135.3 ± 7.0) and negative control group (125.3 ± 7.5, P < 0.05). The colony formation inhibition rate was (7.40 ± 0.94)% in the negative control group and (72.4 ± 6.09)% in the FOXM1 siRNA transfection group. FOXM1siRNA transfection induced cell cycle arrest at G2/M phase with a percentage of (55.6 ± 4.83)%, significantly higher than that of the blank control [(24.30 ± 1.95)%] and negative control group [(21.3 ± 2.06)%, P < 0.05]. Additionally, the FOXM1siRNA transfection significantly increased the chemosensitivity of A549 cells to AG1478 (P < 0.05). Besides, AG1478 induced expression and nuclear relocation of FOXO3a. After the FOXO3a siRNA transfection, the expression of FOXM1 protein was significantly up-regulated, and resulted in a reduction of AG1478-induced inhibition of FOXM1. CONCLUSIONS: The expression of FOXM1 is down-regulated by AG1478 via FOXO3a in the NSCLC cell lines, and then increases the chemosensitivity of A549 cells to AG1478. It suggests that FOXM1 could be a potential target for the therapy and drug exploitation for NSCLC.
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Adenocarcinoma/metabolismo , Factores de Transcripción Forkhead/metabolismo , Neoplasias Pulmonares/metabolismo , Quinazolinas/farmacología , Tirfostinos/farmacología , Adenocarcinoma/patología , Apoptosis , Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Receptores ErbB/antagonistas & inhibidores , Proteína Forkhead Box M1 , Proteína Forkhead Box O3 , Factores de Transcripción Forkhead/genética , Humanos , Neoplasias Pulmonares/patología , Quinazolinas/administración & dosificación , ARN Mensajero/metabolismo , ARN Interferente Pequeño/genética , Transfección , Tirfostinos/administración & dosificaciónRESUMEN
OBJECTIVE: To investigate the relationship between EGFR activation and down-regulation of miRNA-145 in lung cancer. METHODS: Normal human lung epithelia cell line (BEAS-2B), human lung adenocarcinoma cell lines with wild-type EGFR (A549 and H292) and human lung adenocarcinoma cell lines with EGFR mutation (H1975 and H1650) were chosen in this study. The levels of miRNA-145 and p-EGFR were determined by quantitative real-time PCR (qRT-PCR) and Western blotting, respectively, and the relationship between p-EGFR and miRNA-145 levels was analyzed. The miRNA-145 levels were determined by qRT-PCR after activating EGFR with EGF or blocking EGFR signal pathway with AG1478. In addition, ERK1/2 inhibitor U0126 was used to inhibit ERK1/2 activation and then the expression of miRNA-145 was detected. RESULTS: The miRNA-145 levels were closely negatively related with p-EGFR in lung cancer cells (r = -0.926, P = 0.024). EGF down-regulated miRNA-145 expression, particularly in BEAS-2B cells (53.0%; t = 30.993, P = 0.001) and A549 cells (42.6%; t = 14.326, P = 0.005).The miRNA-145 was up-regulated after inhibiting p-EGFR with AG1478, and significantly enhanced by 67.5% in H1975 cells when treated with AG1478 (t = 8.269, P = 0.014). The ERK1/2 signal pathway was activated by p-EGFR. U0126 restored the miRNA-145 down-regulation induced by EGFR-activation in lung cancer cells. CONCLUSION: The activation of EGFR down-regulates miRNA-145 expression through ERK1/2 in lung cancer cells.
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Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Receptores ErbB/metabolismo , Neoplasias Pulmonares/metabolismo , Sistema de Señalización de MAP Quinasas , MicroARNs/metabolismo , Butadienos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular , Línea Celular Tumoral , Regulación hacia Abajo , Activación Enzimática/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Factor de Crecimiento Epidérmico/farmacología , Células Epiteliales/metabolismo , Receptores ErbB/antagonistas & inhibidores , Humanos , Pulmón/citología , Neoplasias Pulmonares/patología , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Nitrilos/farmacología , Fosforilación , Quinazolinas/farmacología , Tirfostinos/farmacologíaRESUMEN
Hsp60sp, a signal peptide derived from the leader sequence of heat shock protein 60 kDa (Hsp60), is a Qa-1/HLA-E-binding peptide. We previously showed that Hsp60sp-specific CD8+ T cells are involved in the immunoregulation of autoimmune diseases by controlling the response of self-reactive lymphocytes. Here, we report that Hsp60sp-specific CD8+ T cells killed malignant lymphocytes in vitro independently of transporter associated with antigen processing (TAP) and classical MHC-I expression. Induction of this cytotoxic T lymphocyte (CTL) response in vivo, either by adoptive transfer of in vitro-amplified CTLs or peptide-loaded dendritic cell immunization, resulted in effective control of lymphoid tumors, including TAP- or classical MHC-I-deficient cells. Hsp60sp-specific immune activation combined with programmed cell death protein 1 (PD-1) blocking synergistically restrained mouse lymphoma development. Importantly, Hsp60sp-specific CD8+ T cells did not negatively affect normal tissues and cells. Our data suggest that Hsp60sp-based immunotherapy is an inviting strategy to control lymphoid malignancies.
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Linfocitos T CD8-positivos/inmunología , Chaperonina 60/química , Células Dendríticas/inmunología , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Linfoma/terapia , Proteínas Mitocondriales/química , Señales de Clasificación de Proteína/fisiología , Linfocitos T Citotóxicos/inmunología , Animales , Presentación de Antígeno , Linfocitos T CD8-positivos/trasplante , Línea Celular , Chaperonina 60/inmunología , Terapia Combinada , Células Dendríticas/trasplante , Femenino , Antígenos de Histocompatibilidad Clase I/metabolismo , Inhibidores de Puntos de Control Inmunológico/farmacología , Inmunización , Linfoma/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Proteínas Mitocondriales/inmunología , Linfocitos T Citotóxicos/trasplanteRESUMEN
PURPOSE: Pancreatic cancer is a lethal disease and usually is diagnosed at advanced stages of disease. This study assessed the effects of intratumoral ethanol injection using an endoscopic ultrasound (EUS) probe on the control of pancreatic cancer in a mouse orthotopic xenograft model. MATERIALS AND METHODS: The subcutaneous and orthotopic human pancreatic cancer cell mouse xenograft models were established. Different concentrations of ethanol (0-95%) were injected into subcutaneous xenograft tumors. In the orthotopic tumor model, ethanol was injected into the tumor lesions under the guidance of a high-frequency EUS probe. Tumor volume, relative tumor volume (RTV), and histopathology were evaluated. The serum amylase level was analyzed at baseline and 24 h after treatment in the orthotopic tumor model. RESULTS: Injection of 40-95% ethanol induced tumor necrosis in the subcutaneous tumor model, while there was no statistical difference between the RTVs of the two groups (P = 0.81). In the orthotopic tumor model, the RTV of the 80% ethanol treatment group was less than that of the saline injection group (P < 0.01); and histologically, there was a large area of necrosis observed in the 80% ethanol group. The serum amylase level was slightly elevated at 24 h after injection and returned to the baseline level at 7 days. CONCLUSION: Injection of 80% ethanol into xenograft tumor lesions of orthotopic pancreatic cancer resulted in tumor necrosis, and the procedure was safe and effective. Future studies will further confirm its antitumor activity as well as assess its safety and feasibility.
RESUMEN
The expression of miR-145 with tumor suppressor function is decreased in lung cancer cells. Epidermal growth factor receptor (EGFR) signaling pathway is abnormally activated in lung cancer cells. It is not clear whether the EGFR signaling pathway is involved in the regulation of miR-145 expression in lung cancer. In the present study, we found that the reduction of miR-145 was associated with EGFR abnormal activation in lung cancer cells. AG1478, an inhibitor of EGFR, may restore the expression of miR-145, indicating that EGFR activation is involved in the downregulation of miR-145 in lung cancer cells. Then, the application of STAT3, AKT and ERK1/2 inhibitors and siRNA against these signaling molecules indicated that ERK1/2 or AKT instead of STAT3 was involved in the process of miR-145 downregulation by EGFR. It was confirmed that AKT through activation of the ERK1/2 signaling molecules mediated the effect of EGFR on miR-145. Furthermore, we found that EGFR downregulated miR-145 through ERK1/2 in lung cancer cells. These findings establish EGFR and miR-145 links in lung cancer cells and therefore contribute to a better understanding of the role of EGFR in lung cancer cells, and provide clues for in-depth study of miR-145 expression and a possible direction for the further increase of miR-145 in lung cancer cells.
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Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Receptores ErbB/metabolismo , Neoplasias Pulmonares/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , MicroARNs/metabolismo , Western Blotting , Carcinoma de Pulmón de Células no Pequeñas/genética , Línea Celular Tumoral , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica/fisiología , Humanos , Neoplasias Pulmonares/genética , ARN Interferente Pequeño , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/fisiología , TransfecciónRESUMEN
FOXM1, a member of the Forkhead transcriptional family, plays an important role in the EMT process, and transforming growth factor-ß1 (TGF-ß1) has been identified as the most potent factor that can independently induce EMT in various types of cancer cells. Here we examine the important role of FOXM1 in TGF-ß1-induced EMT and investigate the mechanism underlying the relationship between TGF-ß1 and FOXM1. Lentivirus-mediated transfection was used to stably upregulate the expression of FOXM1, and a small interfering RNA (siRNA) was introduced to silence the expression of FOXM1. Transwell and wound-healing assays were then performed to assess the invasion and motility potential of non-small cell lung cancer (NSCLC) cells. The NSCLC cell lines exhibited EMT characteristics, including an elongated fibroblastoid shape, induced expression of EMT marker proteins, and increased migratory and invasive potential after induction with TGF-ß1. The overexpression of FOXM1 enhanced TGF-ß1-induced EMT in NSCLC cells. Knockdown of FOXM1 reversed TGF-ß1-induced EMT in NSCLC cell lines but had no effect on the phosphorylation level of ERK. Additionally, U0126, an ERK signaling inhibitor, exerted a reversible effect on TGF-ß1-induced EMT and inhibited FOXM1 expression. FOXM1 regulated by the ERK pathway can mediate TGF-ß1-induced EMT in NSCLC and is a potential target for the treatment of NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Factores de Transcripción Forkhead/metabolismo , Neoplasias Pulmonares/metabolismo , Biomarcadores de Tumor/metabolismo , Butadienos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Movimiento Celular/genética , Transición Epitelial-Mesenquimal/efectos de los fármacos , Transición Epitelial-Mesenquimal/genética , Proteína Forkhead Box M1 , Factores de Transcripción Forkhead/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Pulmonares/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Terapia Molecular Dirigida , Invasividad Neoplásica/genética , Nitrilos/farmacología , ARN Interferente Pequeño/genética , Factor de Crecimiento Transformador beta1/metabolismo , Transgenes/genética , Cicatrización de Heridas/genéticaRESUMEN
Forkhead box M1 (FOXM1), a member of the Fox family of transcriptional factors, is considered to be an independent predictor of poor survival in many solid cancers. However, the underlying mechanism is not yet clear. The aim of the present study was to investigate the clinical significance of the correlation between FOXM1 and epithelial-mesenchymal transition (EMT) in non-small cell lung carcinoma and the possible mechanism responsible for FOXM1-induced EMT and metastasis. In the present study, expression levels of FOXM1 and EMT indicator proteins were determined by tissue microarray (TMA) and immunohistochemical staining, western blotting and reverse transcription-PCR (RT-PCR). Other cellular and molecular approaches including gene transfection, small interfering RNA (siRNA), and migration and invasion assays were utilized. Our results demonstrated that FOXM1 overexpression was statistically significantly associated with a higher TNM stage (p=0.036), lymph node metastasis (p=0.009) and a positive smoking history of the patients (p=0.044). Additionally, high expression of FOXM1 correlated with loss of E-cadherin expression (p<0.001) and anomalous immunopositivity of Vimentin (p=0.002). Moreover, patient survival analysis demonstrated that high expression of FOXM1 (p=0.043) and the presence of lymph node metastasis (p=0.042) were independent prognostic factors for non-small cell lung cancer (NSCLC). Furthermore, various in vitro experiments indicated that overexpression or knockdown of FOXM1 expression altered EMT through activation or inhibition of the AKT/p70S6K signaling pathway. Collectively, the results suggest that FOXM1 may be used as a prognostic indicator for patients with NSCLC and promotes metastasis by inducing EMT of lung cancer cells through activation of the AKT/p70S6K pathway. Therefore, we suggest that FOXM1 may be a potential target for lung cancer therapy.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Factores de Transcripción Forkhead/biosíntesis , Metástasis Linfática/genética , Pronóstico , Anciano , Carcinoma de Pulmón de Células no Pequeñas/patología , Transición Epitelial-Mesenquimal/genética , Femenino , Proteína Forkhead Box M1 , Factores de Transcripción Forkhead/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Proteína Oncogénica v-akt/genética , Proteína Oncogénica v-akt/metabolismo , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Transducción de Señal/genéticaRESUMEN
AIMS: The aim of this study was to investigate the effects of adjuvant chemotherapy cycles on the prognosis of patients with post-operative stomach cancer through retrospective analysis. METHODS: A total of 128 patients with gastric cancer who underwent gastrectomy, followed by adjuvant chemotherapy consisting of epirubicin, cisplatin or oxaliplatin, leucovorin, and 5-fluorouracil, according to a defined schedule, were divided into three groups according to the number of chemotherapy cycles: Group I (<6 cycles); Group II (6 cycles); and Group III (>6 cycles). RESULTS: The 5-year overall survival (OS) was 20.8% in Group I, 45.0% in Group II, and 42.9% in Group III, with a median follow-up of 43 months. The 5-year relapse-free survival (RFS) was 15.1% in Group I, 40% in Group II, and 40% in Group III. The OS and RFS in Groups II and III were significantly better than in Group I (OS, p = 0.002 and p=0.003; RFS, P<0.001 and P=0.002). There was no difference in OS (p = 0.970) or in RFS (p = 0.722) between Groups II and III. Multivariate Cox hazard analysis determined that the number of adjuvant chemotherapy cycles was an independent factor that influenced OS and RFS. CONCLUSION: Six cycles of adjuvant chemotherapy gave encouraging outcomes in patients with resectable gastric cancer. Further prospective randomized controlled investigations are warranted in a multi-center setting.
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Supervivencia sin Enfermedad , Epirrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Gastrectomía , Humanos , Estimación de Kaplan-Meier , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugíaRESUMEN
BACKGROUNDS: Polymorphisms of OPRM1 A118G and ABCB1 C3435T have been suggested to contribute to inter-individual variability regarding pain sensitivity, opioid usage, tolerance and dependence and incidence of adverse effects in patients with chronic pain. This study aimed to investigate the association of both two polymorphisms with opioid requirements in Chinese patients with cancer pain. METHODS: The genotypes of rs1799971 (OPRM1) and rs1045642 (ABCB1) were determined by PCR-RFLP and direct sequencing methods respectively in 112 patients with cancer-related pain. Comparisons between the different genotype or allele groups were performed with t-tests or one-way ANOVA tests, as appropriate. The potential relationship of allele number with opioid response was performed with a trend Jonckheere-Terpstra test. RESULTS: In the 112 subjects, the frequencies of variant 118 G and 3435T allele were 38.4% and 37.9%, respectively. Significant higher 24h-opioid doses were observed in patients with GG (P=0.0004) and AG + GG (P=0.005) genotypes than the AA carriers. The dominant mutant 118G allele tended to be associated with progressively increasing 24h-opioiddoses (P=0.001). Compared with CC/CT, patients with ABCB1 TT genotype received higher 24h- and weight-surface area-adjusted-24h- opioids doses (P=0.057 and 0.028, respectively). CONCLUSIONS: The OPRM1 A118G single nucleotide polymorphism (SNP) is a key contributor for the inter-individual variability in opioidrequirements in Chinese cancer pain patients. This may possibly extend to the ABCB1 C3435T SNP.
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Analgésicos Opioides/uso terapéutico , Manejo del Dolor , Dolor/tratamiento farmacológico , Receptores Opioides mu/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Anciano , Secuencia de Bases , China , Femenino , Fentanilo/uso terapéutico , Frecuencia de los Genes , Humanos , Masculino , Persona de Mediana Edad , Morfina/uso terapéutico , Neoplasias/etiología , Dolor/complicaciones , Percepción del Dolor , Polimorfismo de Nucleótido Simple , Análisis de Secuencia de ADNRESUMEN
We investigated the clinical significance of Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) during angiogenesis in non-small-cell lung carcinoma. JAK2, phospho-JAK2 (pJAK2), STAT3, and phospho-STAT3 (pSATA3) were observed in 40/68 (58.8%), 39/68 (57.4%), 49/68 (72.1%) and 40/68 (58.8%) of the cases. The high expression levels of molecules involved in the JAK2/STAT3 signaling pathway were associated with a decreased survival rate. Of the total number of cases, 73.5% were positive for VEGF and 80.9% for bFGF. Microvessel density (MVD), as determined by CD34 staining and morphology, was higher in NSCLC samples with high pJAK2 and pSTAT3 expression, and the patients with high MVD had poor survival status. In addition, the expression of pSTAT3 correlated with VEGF (r=0.593) and bFGF (r=0.519) (p<0.05). Inhibiting JAK2 and knocking down STAT3 both suppressed STAT3 activation and reduced the expression of VEGF and bFGF in A549 and NCI-H292 cells, demonstrating that STAT3 activation was associated with VEGF and bFGF expression in the two human lung carcinoma cell lines. Therefore, STAT3 may be a critical molecular target for powerful intervention in NSCLC anti-angiogenesis therapy.