Effect Of Ppar Alpha Agonist Fenofibrate On Epithelial-interstitial Transformation And Its Mechanism In A549Cells Line

Objective:To investigate the effects of Peroxisome Proliferator-activated Receptora agonists fenofibrate on Epithelial-interstitial transformation and the Possible mechanism in A549Cells Line.Methods:The proliferation of lung adenocarcinoma cell line A549cultured in vitro were divided into4groups randomly:1The control group,2The fenofibrate group,3The Cisplatin group,4The fenofibrate and Cisplatin Combined treatment group.To assess the sensitivity of A549cells,A549cells were exposed to fenofibrate,Cisplatin and fenofibrate Combined with Cisplatin respectively in48h. MTT was employed to investigate proliferation. Flow cytometry with PI stain was used to detect the cell cycle of A549cells. Wound healing test and Transwell chamber were used to detect the effect of drug intervention on the migration and metastatic ability of A549cells.and E-cadherin/Snail mRNAs and proteins in A549cells were be evaluated by RT-PCR and Weatern-Blot.Result:1Compared with either fenofibrate or Cisplatin alone,combining fenofibrate with Cisplatin increase the growth inhibition rate of A549cells(all P<0.05),2more apoptotic cell were be detected in Combined treatment group than Separate treatment group by flow cytometry (all P<0.05).3Compared with the negative, fenofibrate Combined with Cisplatin could obviously inhibit the proliferation of A549and reduce the migration and metastatic ability of A549cells than either fenofibrate or Cisplatin alone.(all P<0.05),4Compared with the negative, RT-PCR and Weatern-Blot results show Combined treatment group could make the expression of E-cadherin up regulation and expression of Snail down regulation than Separate treatment group.(all P<0.05)Conclusion:our findings suggested that Compared with the negative and the Separate group,Obviously,Peroxisome Proliferator activated Receptor a agonists fenofibrate combined with Cisplatin could inhibit the proliferation of human lung cancer A549cell in vitro.fenofibrate Combined with Cisplatin could decreases the migration and metastatic ability of A549cells.and have a synergistic effect on Epithelial-interstitial transformation of A549cells. these effect could be related with up regulating the expression of E-cadherin and down regulating the expression of Snail.This study explored the clinical treatment of lung cancer treatment ideas and a new combination of drugs, laid the foundation for further study.