摘要
目的体外研究Hedgehog(HH)信号通路阻断剂Cyclopamine和抗血管生成剂YH-16对胰腺癌细胞株BxPC-3的抑制作用。方法以Cyclopamine和YH-16单独或联合干预BxPC-3细胞,MTT法观察药物对肿瘤细胞生长的影响,流式细胞仪检测细胞凋亡,RT-PCR法检测细胞凋亡相关蛋白Bcl-2和Bax的表达情况。结果Cyclopamine和YH-16对BxPC-3细胞均有明显的抑制作用,两者联合作用时抑制作用更强(P<0.05)。Cyclopamine和YH-16均可诱导细胞凋亡,联合作用后细胞的凋亡率更高(P<0.05)。Cyclopamine和YH-16均可下调Bcl-2和上调Bax的表达,联合用药则下调Bcl-2和上调Bax更明显(P<0.05)。结论Cyclopamine和YH-16能抑制BxPC-3肿瘤细胞的增殖,诱导细胞凋亡,两者联合作用时抑瘤效果明显增加,其机制可能与调控凋亡相关蛋白Bcl-2、Bax的表达有关。
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.
出处
《西安交通大学学报（医学版）》
CAS
CSCD
北大核心
2010年第3期283-287,共5页
Journal of Xi’an Jiaotong University（Medical Sciences）
基金
陕西省科学技术研究发展计划项目(No.2008k09-04)~~
