| Lung cancer is an abbreviation of primary bronchogenic carcinoma, of which 85% is non small cell lung cancer (NSCLC). In September 2011, the dates from World Health Organization(WHO) showed that the number of people who were diagnosed as lung cancer was 16.1 million around the world and accounted for 13% of the total number of cancer patients in 2008. The incidence of patients who are lung cancer is increasing at 26.9% per year in china, if invalidity control measures were not taken right now,1 million lung cancer patients will be reached in 2025. Particularly, the standardization mortality rate of lung cancer in Xuanwei city of Yunnan province was 0.83‰ which was 4.11 times more than that of national average.A process which epithelial cells lose the characteristics, such as cell polarity and cells adhesion, and gain the abilities which can move and permeate to nearby tissues and become mesenchymal cells is called as epithelial mesenchymal transformation (EMT). There are closely relationships between EMT and tumor metastasis, no sensitive to chemotherapy drugs, cancer stem cells. Many extracellular signal molecules participate in tumor EMT such as Notch, Hedgehog, TGF-β, RTK, Wnt and so on. At present, EMT is a hot research spot for the prevention and treatment of tumor. Large number of studies have indicated that EMT widely existed in patients with lung cancer, and also played important roles in neoplasm metastasis, drug resistance and cancer stem cell.At present, lots of natural effective ingredients and chemical compounds were discovered have inhibitory effects on EMT of tumor based on the characteristics of rich structures and targets of it, such as extracts of scutellaria baicalensis and fritillaria cirrhosa, celastrus orbiculatus ethyl acetate extracts, osthole, resveratrol, luteolin and so on. Scutellaria baicalensis is a perennial labiatae herbaceous plants, and use roots for medicine in traditional chinese medicine(TCM). Lung cancer belongs to lung jam, cough, hemoptysis, chest pain and so on which was based on theoretical knowledge of TCM. Many prescriptions of TCM for treating lung cancer frequently by using the removing heat from lung characteristics of scutellaria baicalensis. Up to now, many studies have shown that the main pharmacological mechanism of scutellaria baicalensis on lung cancer were inducing cell apoptosis, inhibiting cell proliferation, sensitizing cancer cell to drugs and hindering cancer cell movement and so on. Neoplasm metastasis, drugs resistance, and recurrence are the primary causes for treatment failure of lung cancer, and EMT are involved in them. At present, whether scutellaria baicalensis has impact on EMT of lung cancer which has not been reported.This research intends to study the influence of total flavonoids extracts of scutellaria baicalensis on lung cancer A549 cell EMT induced by TGF-β1.At first, using TGF-β1 induce lung cancer A549 cell happen EMT, and then intervented by total flavonoids extracts of scutellaria baicalensis, and study the effect of it through assay of MTT, wound healing, cell invasion and PT-PCR analysis. Meanwhile, We also further study whether it has influence on lung cancer A549 cell which may effacted on cisplatin resistance, migration and invasion by induced EMT.The results of this study showed that the IC50 value of total flavonoids extracts of scutellaria baicalensis treating A549 cell for 72 hours in no TGF-β1 induced group and TGF-β1 induced group respectively was 48.790ug/ml and 43.178ug/ml (P=0.0393). There was significant difference between no TGF-β1 induced group and TGF-β1 induced group for cell proliferation inhibition of total flavonoids extracts of scutellaria baicalensis in 50ug/mL (P<0.05), but not in other concentrations (P> 0.05), The IC50 of cispatin treating lung cancer A549 cell for 48 hours in no TGF-β1 induced group, TGF-β1 induced group and TGF-β1 induced group combined with 50ug/ml total flavonoids extracts of scutellaria baicalensis respectively was 2.993ug/ml, 3.314ug/ml and 2.434ug/ml (P=0.0025). Comparing to no TGF-β1 induced group and TGF-Pi induced group, the IC50 value of cisplatin in TGF-β1 induced group combined with 50ug/ml total flavonoids extracts of scutellaria baicalensis were significantly decreased by 18.68% and 26.55%(P<0.05), respectively. Though there were no significant differences between no TGF-β1 induced group and TGF-β1 induced group at IC50 value of cisplatin (P>0.05), total flavonoids extracts of scutellaria baicalensis could increase the sensitivity of lung cancer A549 cells to cisplatin in its concentration 2～4 ug/ml regardless of whether it happened EMT, while strangely act an opposite function in 0～1ug/ml and 6～8ug/ml. And then, total flavonoids extracts of scutellaria baicalensis also inhibited lung cancer 549 cell migration and invasion in concentration dependence, and there were no significant differences between no TGF-β1 induced group and TGF-β1 induced group (P>0.05). At last, The flavonoids extracts of scutellaria baicalensis could reverse A549 cell EMT induced by TGF-β1 through decreasing epithelial cell marker protein E-cadherin and increasing mesenchymal cell marker protein Vimentin mRNA expression in concentration dependence.In conclusion, the flavonoids extracts of scutellaria baicalensis have an inhibitory effect on lung cancer A549 cell EMT induced by TGF-β1, may through decreasing E-cadherin and increasing Vimentin mRNA expression, and it also inhibits the moving and permeating ability of lung cancer 549 cell no matter whether lung cancer 549 cell happens EMT in concentration dependence, and it can increase the sensitivity of lung cancer A549 cells to cisplatin in its concentration 2～4 ug/ml.Pathologic TNM classification, age, gender, and tumor cell types are important factors which influence the clinical outcomes of NSCLC patients. EMT was frequently happened in tumor formation, invasion, metastasis, recurrence and drugs resistance, and its biological key regulation factors could provide important clinical markers for outcomes prediction. Lower expression of epithelial marker protein E-cadherin was bad for overall survival(OS) of patients with lung cancer, and it had closely correlations with differentiation of tumor, movement to lymph node, invasion to vascular and the classifications of TNM. With increasing studies about the impact of mesenchymal marker protein Vimentin expression on the prognosis of patients with NSCLC, while conflicting results was among them, and there was no meta analysis article for the impact of Vimentin expression on the prognosis of NSCLC patients at home and abroad up to now.Therefore, this study according to the medthods of Cochrane systematic evaluation and meta analysis for the influcence on OS and disease free survival(DFS) of patients with NSCLC whoes tumor tissues was detected the level of Vimentin expression by using immunohistochemical, and to provide something references for it’s clinical application. Papers which were related to the correlations between Vimentin expression and the prognosis of patients with NSCLC were researched by prospective cohort study in databases covering CNKI, Wang Fang, VIP, CMB, Embase, Elsevier SD, PUBMED, the Cochrane Library, the clinical trail, Web of Science and Medline from each establishment dates to February 2,2015. The included studies which were removed the duplicates based on the criterias of including and excluding, cross-checked, assessed and then merged the result. The meta analysis of this study was done by the Stata 12.0 software, and 9 articles including 9 trials(n=1 302)were included. The results of meta analysis predicted that higher Vimentin expression was a bad factor of outcome prediction for NSCLC patients on OS and DFS, the merging hazard ratio (HR) respectively was HR=2.04,95%CI(1.57,2.66), P <0.001 and HR= 1.56,95%CI(1.20-2.04), P=0.001; Begg’s and Egger’s test showed that no bias of publication was existed among them; and our result was stable proved by sensitivity analysis. Therefore, higher expression of Vimentin is a risk factor for prognosis of NSCLC patients, while it needs more further large samples studies to prove because the number of our study included was not enough. |
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