Effects of bortezomib on growth inhibition of pancreatic cancer cells BxPC3 and SW1990 in vitro

Objective To investigate the effect of bortezomib on proliferation and apoptosis of pancreatic cancer cell lines BxPC3,SW1990 and explore possible mechanisms of bortezomib's killing effect on cancer cells.Methods BxPC3,SW1990 cells were treated by using 1,10,50,100,500 nmol/L and 1,10 μmol/L of bortezomib,and cells without bortezomib treatment were considered as control group.The cell proliferation was determined by MTF assay,and apoptosis was determined by flow cytometry.Bak,Bax,Bcl2,Bcl-xl,survivin mRNA expressions were measured by RT-PCR,and Western blot was applied to determine the expressions of pro-caspase-3,cleaved-caspase-3,Bax,Bcl-2,surviving protein.Results When bortezomib concentration was higher than 50 nmol/L,it inhibited the proliferation of two cell lines in a dose and time-dependent manner.And with the same treatment the rate of proliferation inhibition of BxPC3 cells by bortezomib was greater than that of SW1990 cells,and the difference between the two cell lines was statistically significant (P ＜0.05).Apoptosis rates in the groups of BxPC-3 and SW1990 cells treated by 100 nmol/L bortezomib were (22.56 ± 4.23) ％ and (12.71 ± 2.23) ％,which were significantly higher than those in control group (2.15 ± 0.47) ％ and (2.32 ± 0.54) ％,P ＜ 0.05).In addition,apoptosis rate of BxPC3 cells was significantly higher than that of SW1990 cells (P＜0.05).Bak mRNA expression of BxPC3 and SW1990 cells after 100 nmol/L bortezomib treatment were not significantly changed,but the expression of Bax mRNA and protein was significantly increased (P ＜0.05).Bcl-2 mRNA and protein,as well as Bcl-xl mRNA expressions was significantly decreased (P ＜0.05).The expression of survivin mRNA and protein in BxPC3 cells were decreased,but were increased in SW1990 cells(P ＜0.05).The expression of pro-caspase-3 protein in the two cell lines was decreased,while the expression of cleaved-caspase-3 protein was increased (P ＜0.05).Conclusions Bortezomib can inhibit the proliferation of pancreatic cancer cell Iines BxPC-3 and SW1990 and induce apoptosis,and the effect on BxPC3 cells is more than that on SW1990 cells.The mechanism may depend on activation of the mitochondrial pathway of apoptosis,and be related to survivin-involved drug-resistance. Key words: Pancreatic neoplasms;  Bortezomib;  Cell line, tumor;  Cell proliferation; Apoptosis