The Experimental Study Of Fenofibrateinhibited Pancreatic Cancer Cells Proliferation Via Activation Of P53 Mediated By Upregulation Of LncRNA MEG3

ObjectTo explore the effect of long noncoding RNA MEG3 on fenofibrate's anti-proliferation of pancreatic cancer cells.Methods1,Pancreatic cancer cell lines PANC-1 and SW1990 were treated with fenofibrate at different concentrations for different durations.The effect of fenofibrate on cell proliferation was evaluated by MTT and colony formation assays.2.A commercial human LncRNA microarray was applied to investigate the changes of LncRNA expression profiles of PANC-1 cells treated with fenofibrate.3.Using RT-PCR to confirm the changes of MEG3 expression in PANC-1 after treated with fenofibrate.Transfecting PANC-1 cells with MEG3-SiRNA and detecting the changes of MEG3 expression by RT-PCR after transfection.Using MTT and Western Blot to detect cell proliferation and p53 expression of SiRNA PANC-1 cells after treated with fenofibrate.4.Transfecting PANC-1 cells with pcDNA3.0-MEG3 and using RT-PCR to investigate the changes of MEG3 expression.MTT and colony formation assay were applied to detect cell proliferation after transfection.Using Western Blot to detect changes of p53 after transfection.Results1.Fenofibrate inhibited more than 50%cell growth both in PANC-1 and SW1990 at the concentration of 100?M for 48h treatment,and PANC-1 was more sensitive to fenofibrate than SW1990.2.Human LncRNA microarray analysis showed increased MEG3 expression and p53 pathway was activated at the same time.3.MEG3 expression in PANC-1 cells was upregulated after fenofibrate treatment.Transfection with MEG3-SiRNA leaded to MEG3 decreation.After treating with fenofibrate,cell proliferation was increased in SiRNA PANC-1 cells,and the level of p53 was decreased.4.After transfection with pcDNA3.0-MEG3,MEG3 was over-expressed.Cell viability was decreased and p53 level was reduced after transfection.Conclusions1.Fenofibrate inhibited proliferation of pancreatic cancer cell lines PANC-1 and SW1990.2.MEG3 expression in PANC-1 cells was upregulated after treating with fenofibrate,and p53 pathway was activated.3.Knockdown of MEG3 significantly attenuated fenofibrate's anti-proliferation in PANC-1 cells and p53 level was decreased.Meanwhile,over-expression of MEG3 enhanced PANC-1 cell death and increased p53 expression.Our findings indicated that fenofibrate can inhibite pancreatic cancer cells proliferation via activation of p53 mediated by upregulation of LncRNA MEG3.