Inhibitory effect of cyclopamine combined with YH-16 on human pancreatic cancer cell line BxPC-3

Objective: To explore the inhibitory effect of Hedgehog signal pathway blocker cyclopamine combined with YH-16 on human pancreatic cancer cell line BxPC-3 in vitro. Methods: BxPC-3 cells were treated with cyclopamine, YH-16 or a combination of the two drugs, respectively. The growth curves of cells in each group were obtained by MTT assay. The cell apoptosis was examined by Annexin-V/PI flow cytometry. We observed the effect of cyclopamine combined with YH-16 on Bcl-2 and Bax mRNA expressions detected by RT-PCR. Results: Cyclopamine and YH-16 obviously suppressed the growth of BxPC-3 cells in dose- and time-dependent manners. Cyclopamine combined with YH-16 resulted in greater growth inhibition than used alone (P < 0.05). Both cyclopamine and YH-16 induced apoptosis of BxPC-3 cells. Furthermore, a combination of the two drugs led to a higher apoptosis rate (P<0.05). Cyclopamine or YH-16 alone down-regulated Bcl-2 expression and up-regulated Bax expression at the mRNA level. The combination of the two drugs could enhance the inhibitory effect significantly (P<0.05). Conclusion: Cyclopamine and YH-16 can inhibit the proliferation of BxPC-3 cells and lead to their apoptosis. Moreover, cycloppamine combined with YH-16 increases the inhibitory effect, which might be related to the regulation of apoptosis-related proteins Bcl-2 and Bax.