The effect of signal transducer and avtivator of transciption 3 gene silencing on the proliferation of pancreatic cancer cell lines and their sensitivity to gemcitabine

Objective To determine the effect of signal transducer and avtivator of transciption 3 (STAT3) gene silencing on the sensitivity of pancreatic cancer cell lines to gemcitabine,and investigate its effect on gemcitabine induced pancreatic cancer cell proliferation and apoptosis.Methods Six human pancreatic cancer cell lines (BxPC-3,L3.6pl,CFPAC-1,MPanc-96,PANC1 and MiaPaCa-2) and human pancreatic ductal epithelial (HPDE)cell line was transfected with STAT3 luciferase lentiviral,and renilla luciferase lentivirus as control.The levels of STAT3 and pSTAT3 protein were detected by Western blotting.STAT3 gene expression of pancreatic cancer cell lines was silenced by RNA interference,and the expression level of STAT3 protein was detected by Western blotting.The proliferation was determined by MTS method and apoptosis was measured by flow cytometry.Results The expression levels of STAT3 and pSTAT3 protein in 6 human pancreatic cancer cell lines were significantly higher than that in HPDE cells,but the expression levels were not associated with resistance and sensitivity to gemcitabine.The expression levels of STAT3 protein of BxPC3,MiaPaCa-2,PANC1,L3.6pl,CFPAC-1,MPanc-96 cells with STAT3 gene silencing were 0.40 ± 0.04,0.09 ±0.01,0.38 ±0.02,0.27 ±0.06,0.10 ±0.02,0.24 ±0.04,which were lower than those in siRNA-control group (2.27 ± 0.21,1.83 ± 0.12,2.27 ± 0.17,2.23 ± 0.21,0.33 ± 0.05,1.24 ± 0.19,P ＜0.05),however,it had no significant effect on cell proliferation and apoptosis.Silencing of STAT3 could sensitize all 6 cell lines to gemcitabine,and the killing effect of gemcitabine increased by 10％ ～ 15％.Conclusions There is no obvious relationship between STAT3 expression level and chemoresistance of pancreatic cancer cells.STAT3 silencing can sensitize cell lines to gemcitabine. Key words: Pancreatic neoplasm;  RNA interference;  Signal transducer and activation of transcription