Effect of bortezomib in combination with valproate on growth inhibition of human pancreatic cancer cell line SW1990 in vitro

Abstract

Objective To investigate the effect and mechanism of bortezomib in combination with valproate on human pancreatic cancer cell line SW1990. Methods Bortezomib, valproate were tested alone and in combination for their abilities to inhibit SW1990 cell line proliferation by methyl thiazol tetrazolium(MTT). The early apoptosis of SW1990 cell line were detected by Annexin V/propidium iodide(PI) double staining method, and the expression of Survivin and Caspase-3 mRNA were detected by reverse transcriptase-polymerase chain reaction(RT-PCR). The content of Survivin and pro-Caspase-3 and cleaved-Caspase-3 were evaluated by Western blotting. Results Bortezomib could inhibited faintly the proliferation of SW1990 cell line, however, valproate and combination could inhibited effectively the proliferation of SW1990 cell line. The early stage apoptosis rate of SW1990 cells was(13.47±2.21)% when treated with bortezomib, and was (26.73±2.36)% when treated with valproate,and was(47.06±2.76)% when they were treated with bortezomib combined with valproate. The expression of Survivin mRNA and proteins had no significant changes in bortezomib group. The expression of Survivin, Caspase mRNA and proteins levels were down-regulated in valproate and combination group. Comparisons of treated groups and control group have significant difference (P<0.05)and comparisons of combination groups and single drug group have also significant difference(P< 0.05). Conclusion Bortezomib interacts synergistically with valproate to induce apoptosis in SW1990 cell line. The potential mechanism is down-regulated Survivin mRNA and protein levels to promote apoptosis of cells. Key words: Bortezomib; Valproate; Pancreatic neoplasms; Apoptosis