In vitro effect of erlotinib on the growth of pancreatic cancer cell line BxPC3 and its mechanism

Objective To investigate the effect and possible mechanism of erlotinib,an epidermal growth factor recceptor inhibitor,on human pancreatic cancer cell lines BxPC3 in vitro.Methods Methyhhiazolyhetrazolium(MTT)assay was used to detected the proliferation of BxPC3 after exposure to erlotinib,apoptosis and cell cycle changes were studied by flow eytometry and terminal deoxynucleotidyl transferase-mediated nick end labeling assay(TUNEL).The expressions of bcl-2 mRNA,bax mRNA,bcl-xL mRNA and bak mRNA were determined by reverse transcriptase polymerase chain reaction(RT-PCR). Results Edotinib inhibited BxPC3 cells growth in a dose and time dependent manner in vitro.The cell viabilities in erlotinib 1 μmol/L and 100 μmol/L groups 72 h later were(90.25 ±2.62)%and(40.75 ±2.98)%,and the difference was statistically significant(P<0.01).The cell viability in edotinib 50 μmol/L groups 24 h and 96 h after BxPC3 exposure were(74.0±4.08)%and(49.50 ±1.29)%,and the difference was statistically significant(P<0.01).Cell apoptosis rate in erlotinib 50 μmol/L group was(11.0 μ1.1)%,which was significantly higher than(6.2 ±1.1)%in control group(P<0.01).G_0/G_1 cell accounted for (73.4±1.3)%of all the cells,which was significantly higher than(63.3 ±1.O)%in control group.With transmission electron microscope,the morphology of BxPC3 ceils showed typical apoptosis and apoptotic body. The expressions of bcl-2 mRNA,bel-xl mRNA were down-regulated,while the expression of bax mRNA was slightly up-regulated,and the expression of bak mRNA was not affected.Conclusions The growth of BxPC3 cells could be suppressed by erlotinib and possible mechanisms involved blocking cell cycle,up-regulating apoptosis proteins and down-regulating apoptosis inhibitor proteins. Key words: Pancreatic neoplasms; Receptor,epidermal growth factor; Apoptosis; Erlotinib