Mechanism of Fuzheng Qudu prescription in the treatment of lung cancer based on network pharmacology and experimental validation.

Objective: This research utilized network pharmacology to investigate the potential of Fuzheng Qudu prescription (FZQDP) in treating lung cancer (LC). Methods: The components and their targets of FZQDP were analyzed for their relationship with LC-related targets using bioinformatics tools. Mouse Lewis lung carcinoma (LLC) cells were cultured in vitro and treated with FZQDP or cisplatin (DDP) before applying the MTT assay to determine FZQDP concentrations, and the IC50 value. According to the IC50 value, the effect of FZQDP on apoptosis and cell cycle was detected by flow cytometry. Mouse tumor growth was recorded using live animal imaging, and measurements of tumor and spleen weight were used to calculate the tumor inhibition rate and spleen index. The effects on mouse liver and kidneys were observed by analyzing levels of AST, ALT, BUN, and CRE in blood and hematoxylin and eosin (H & E) stained sections. Additionally, levels of IL-2, IL-10, IL-6, and IFN-γ in serum, along with the frequencies of CD4+ and CD8+ T cells in the spleen, were measured using Mouse multiple Cytokine Assay and flow cytometry, respectively. Results: SRC, STAT3, MAPK3, and MAPK1 could be crucial targets of FZQDP in the treatment of LC. FZQDP demonstrated inhibition of LC cell proliferation and tumor growth, as well as enhancement of apoptosis and induction of G2 phase cell cycle arrest. Furthermore, FZQDP led to elevated levels of IL-2 and IFN-γ, increased frequencies of CD4+ T cells and decreased levels of IL-6 and IL-10. Importantly, FZQDP did not exhibit any noticeable hepatotoxic or nephrotoxic effects in mice. Conclusion: FZQDP may target multiple signaling pathways to treat LC. In a LC mouse model, FZQDP was found to inhibit tumor growth and improve immune function.

Scorpiones, Scolopendra and Gekko Inhibit Lung Cancer Growth and Metastasis by Ameliorating Hypoxic Tumor Microenvironment via PI3K/AKT/mTOR/HIF-1α Signaling Pathway.

OBJECTIVE: To investigate whether Buthus martensii karsch (Scorpiones), Scolopendra subspinipes mutilans L. Koch (Scolopendra) and Gekko gecko Linnaeus (Gekko) could ameliorate the hypoxic tumor microenvironment and inhibit lung cancer growth and metastasis by regulating phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin/hypoxia-inducible factor-1α (PI3K/AKT/mTOR/HIF-1α) signaling pathway. METHODS: Male C57BL/6J mice were inoculated with luciferase labeled LL/2-luc-M38 cell suspension to develop lung cancer models, with rapamycin and cyclophosphamide as positive controls. Carboxy methyl cellulose solutions of Scorpiones, Scolopendra and Gekko were administered intragastrically as 0.33, 0.33, and 0.83 g/kg, respectively once daily for 21 days. Fluorescent expression were detected every 7 days after inoculation, and tumor growth curves were plotted. Immunohistochemistry was performed to determine CD31 and HIF-1α expressions in tumor tissue and microvessel density (MVD) was analyzed. Western blot was performed to detect the expression of PI3K/AKT/mTOR/HIF-1α signaling pathway-related proteins. Enzyme-linked immunosorbent assay was performed to detect serum basic fibroblast growth factor (bFGF), transforming growth factor-ß1 (TGF-ß1) and vascular endothelial growth factor (VEGF) in mice. RESULTS: Scorpiones, Scolopendra and Gekko prolonged the survival time and inhibited lung cancer metastasis and expression of HIF-1α (all P<0.01). Moreover, Scorpiones, Scolopendra and Gekko inhibited the phosphorylation of AKT and ribosomal protein S6 kinase (p70S6K) (P<0.05 or P<0.01). In addition, they also decreased the expression of CD31, MVD, bFGF, TGF-ß1 and VEGF compared with the model group (P<0.05 or P<0.01). CONCLUSION: Scorpiones, Scolopendra and Gekko all showed beneficial effects on lung cancer by ameliorating the hypoxic tumor microenvironment via PI3K/AKT/mTOR/HIF-1α signaling pathway.

Drug monomers from Salvia miltiorrhiza Bge. promoting tight junction protein expression for therapeutic effects on lung cancer.

Salvia miltiorrhiza Bge. is a traditional Chinese medicine (TCM) that has been used for treatment of various diseases, including cancer by activating blood circulation and removing blood stasis. Tanshinone (TanIIA) and cryptotanshinone (CPT) are major lipophilic compounds extracted from the root of Salvia miltiorrhiza Bge., which are considered to be the effective compounds affecting the efficacy of the anti-tumor therapy of Salvia miltiorrhiza Bge. We have explored the mechanism of CPT and TanIIA exerting inhibition in non-small cell lung cancer (NSCLC) to provide experimental data support for guiding the translational development and clinical application of anti-tumor components of TCM. The subcutaneous tumor model and in vitro culture model of A549 cells was constructed to evaluate CPT and TanIIA's tumour-inhibitory effect respectively. RNA sequencing (RNA-seq) and bioinformatics analysis were conducted to identify differentially expressed genes (DEGs) and signalling pathways related to CPT and TanIIA treatment. qRT-PCR and Western blot were used to explore the mechanism of CPT and TanIIA intervention on NSCLC. Both CPT and TanIIA significantly inhibited the proliferation of A549 tumor cells and tumor growth in animal models. After intervention, the migration ability decreased and the level of apoptosis increased. RNA-seq results showed that both CPT and TanIIA could cause gene differential expression, miR-21-5p as one of the most significant gene expression differences between the two groups, and could act on cell connectivity. CPT and TanIIA play a regulatory role in regulating tight junction proteins (Occludin and ZO1), and Occludin mRNA and protein levels were reduced in an in vitro miR-21-5p overexpression A549 cell model. The mechanisms may be related to the reduction of miR-21-5p expression to increase the level of promoted tight junction protein expression for the purpose of inhibiting proliferation and invasion of NSCLC.

Prognostic role of snail in lung cancer: Protocol for a systematic review.

BACKGROUND: Increasing studies were performed to explore the prognostic value of snail in lung cancer (LC), however, with inconsistent results. Hence, this systematic review is aimed to evaluate the prognostic role of snail in patients with LC. METHODS: A comprehensive literature search in the PubMed, Embase, the Cochrane Library, and Web of Science databases will be conducted to identify eligible studies. Language is limited as English. We will employ hazard ratios (HRs) and 95% confidence intervals (95% CIs) to estimate the correlations between snail expression and overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), disease-free survival (DFS), and clinicopathological features. Meta-analysis will be performed using STATA 14.0 software. RESULTS: This study will provide a high-quality synthesis of current evidence of the correlations between snail expression and OS, PFS/RFS/DFS, and clinicopathological features. CONCLUSION: The study will provide updated evidence to assess whether the expression of snail is in association with poor prognosis in patients with LC. ETHICS AND DISSEMINATION: It is not necessary for ethical approval because individuals cannot be identified. The protocol will be disseminated in a peer-reviewed journal or presented at a relevant conference. PROSPERO REGISTRATION NUMBER: This systematic review protocol has been registered in the PROSPERO network (No. CRD42018095191).

Different Survival Benefits of Chinese Medicine for Pancreatic Cancer: How to Choose?

OBJECTIVE: To assess the efficacy of Chinese medicine (CM) on patients with pancreatic cancer (PC) in a retrospective population-based study. METHODS: Between January 1, 2013, and August 30, 2016, according to whether received Western medicine treatment, the patients were included into either integrative medicine (IM) group or CM group. All enrolled patients were orally administrated with Gexia Zhuyu Decoction () or Liujun Ermu Decoction () by syndrome differentiation, twice a day, last for at least 2 months. The primary end point was overall survival (OS). RESULTS: A total of 174 patients with PC were enrolled in this study. In stage I/II, the median OS was 20.5 months in the IM group [95% confidence interval (CI), 12.499 to 28.501] and 11.17 months in the CM group (95% CI, 5.160 to 17.180, P=0.015). The 1- and 2-year survival rates for the two groups were 47.0%, 40.0% and 21.0%, 21.0%, respectively. In stage III/IV, median OS was 13.53 months (95% CI, 8.665 to 18.395) in the IM group versus 6.4 months (95% CI, 0.00 to 15.682) in the CM group, respectively (P=0.32). The 1- and 2-year survival rate for the IM and CM groups were 27.0%, 7.0% and 20.0%, 2.0%, respectively. CONCLUSIONS: Intervention of CM contributes to the different survival benefits for PC in different stages. Multimodality treatment might be a promising strategy for PC patients in early stage. While, in advanced stage, CM might be an alternative candidate for PC patients.

Comprehensive treatment with Chinese medicine in patients with advanced non-small cell lung cancer: A multicenter, prospective, cohort study.

OBJECTIVE: To determine whether additional Chinese medicine (CM) could prolong survival and improve the quality of life (QOL) in patients with advanced non-small cell lung cancer (NSCLC) compared with Western medicine (WM) alone. METHODS: This was a multicenter, prospective cohort study. A total of 474 hospitalized patients with stage III-IV NSCLC were recruited and divided into 2 groups. Patients in the WM group received radiotherapy, chemotherapy, and optimal supportive therapy according to the National Comprehensive Cancer Network (NCCN) guidelines. In the integrative medicine (IM) group, individualized CM (Chinese patent medicines and injections) and WM were administered. The primary end point was overall survival, and the secondary end points were time to disease progression, adverse events, and QOL. Follow-up clinical examinations and chest radiography were performed every 2 months. RESULTS: The median survival was 16.60 months in the IM group and 13.13 months in the WM group (P<0.01). The incidences of loss of appetite, nausea, and vomiting in the IM group were significantly lower than those in the WM group (P<0.05). The QOL based on Functional Assessment of Cancer Therapy-Lung in the IM group was markedly higher than that in the WM group at the fourth course (P<0.05). CONCLUSIONS: Additional CM may prolong survival and improve the QOL patients with NSCLC. The adverse effects of radio- and chemotherapy may be attenuated as CM is used in combination with conventional treatments.

[Safety and effectiveness of large dose compound Sophora flavescens Ait injection in the treatment of advanced malignant tumors].

OBJECTIVE: To evaluate the effectiveness and safety of large dose compound Sophora flavescens Ait injection in the treatment of advanced malignant tumors. METHODS: A non-randomized case control trial was conducted. Ninety six patients with pathologically confirmed advanced non-small-cell lung cancer, gastric cancer and colorectal cancer were divided into traditional Chinese medicine group and chemotherapy group, 48 cases each. Patients of the traditional Chinese medicine group received treatment with large dose of compound Sophora flavescens Ait injection (20 ml/d), and 21 days as a cycle. RESULTS: Forty-seven patients of the traditional Chinese medicine group and 46 patients of the chemotherapy group completed their treatment, respectively. The clinical benefit rate (CBR) in the traditional Chinese medicine group was 83.0%, significantly higher than that in the chemotherapy group (69.6%) (P < 0.01). The Karnofsky performance status and weight improvement in the traditional Chinese medicine group was superior to that in the chemotherapy group (P < 0.05). Except the skin irritation in one patient in the traditional Chinese medicine group, there were no other clinical adverse effects related with the large dose compound Sophora flavescens Ait injection. CONCLUSIONS: Large dose compound Sophora flavescens Ait injection in the treatment of advanced malignant tumors is safe and effective. The recommended dose is 20 ml/d.

[Multi-center randomized clinical study on Shenqi-fuzheng injection combined with chemotherapy in the treatment for lung cancer].

OBJECTIVE: To investigate the effect of Shenqi-fuzheng injection combined with chemotherapy on the quality of life in lung cancer patient. METHODS: 232 pathologically confirmed nonsmall cell lung cancer patients were enrolled into this multi-center randomized trial. Of these 232 patients, 116 cases were treated with chemotherapy alone (chemotherapy group), another 116 with chemotherapy combined with Shenqi-fuzheng injection produced by Lizhu Company (Shenqi-fuzheng group). Life quality of these patients were evaluated using the QOL scale of European Organization for Research on Treatment of Cancer (QLQ-C30) and the functional living index-cancer. RESULTS: Compared with chemotherapy group, Life quality and symptoms were improved in the Shenqi-fuzheng group, which including lassitude, deficient in breath, pain, fullness in chest and hypochondrium, excessive phlegm, cough, complexion whiteness. Response rate to chemotherapy was also improved. No AE and SAE were observed in the Shenqi-fuzheng group. CONCLUSION: Shenqi-fuzheng injection combined with chemotherapy is safe and effective in the treatment for non-small cell lung cancer.