Effects of gemcitabine plus erlotinib on the proliferation of pancreatic cancer cells / 解放军医学杂志

ABSTRACT

Objective To investigate the sequence-dependent effects of gemcitabine plus erlotinib on the proliferation of human pancreatic carcinoma cells,BXPC-3 and PANC-1,and the possible mechanisms involved.Methods The expressions of mRNA and protein of endothelial growth factor receptor(EGFR)were determined by RT-PCR and Western blotting respectively.MTT assay was used to examine the effects of gemcitabine(3?10-11-3?10-2mol/L)and erlotinib(10-8-10-4mol/L),respectively,on the proliferation of human pancreatic carcinoma cells,then the IC50 was calculated subsequently.The effects of gemcitabine(IC50)and erlotinib(10-5mol/L)either administered alone,simultaneously,or sequentially(with 72h or 24h interval)on the proliferation of cells with MTT assay.Cell cycle was detected by flow cytometry.Results Both mRNA and protein of EGFR were expressed in BXPC-3 and PANC-1 cells.Gemcitabine(3?10-10-3?10-2mol/L)and erlotinib(10-6-10-4mol/L)significantly inhibited the proliferation of BXPC-3 and PANC-1 cells in a time-and concentration-dependent manner.The effects of gemcitabine plus erlotinib on cell proliferation were sequence-dependent.The inhibitory effects on cell proliferation was enhanced when administered simultaneously(P=0.034;P=0.049)or erlotinib was administered 24h prior to gemcitabine(P=0.001;P=0.025)in comparison to that of each drug used alone.However,administration of erlotinib 24h after that of gemcitabine(P=0.499,P=0.824)exerted no additive effects on the cell proliferation when compared with the effect of gemcitabine used alone.No statistical difference existed in the inhibitory effects on cell proliferation between the simultaneous administration of both drugs and the gemcitabine administration following erlotinib(P=0.199,P=0.767).Erlotinib plus/or gemcitabine treatment resulted in the block of cell cycle of BXPC-3 cells at G1 phase.Conclusions Both gemcitabine and erlotinib can inhibit the proliferation of BXPC-3 and PANC-1 cells.The concurrent administration or sequential administration of gemcitabine following erlotinib exerts stronger additive effects on cell proliferation than when gemcitabine is used alone.However,the additive effects are not related to the influence of the both drugs on cell cycles.