文档介绍：Cyclopamine联合YH16对人胰腺癌BxPC3细胞的抑制作用
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作者:徐复国,马清涌,郭坤,胡恒通,张珉,沙焕臣,宫晓光
【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()。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()。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()。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。
【关键词】 Cyclopamine;YH16;胰腺癌;细胞增殖;细胞凋亡
ABSTRACT:Objective To explore the inhibitory effect of Hedgehog signal pathway blocker bined with YH16 on human pancreatic cancer cell line BxPC3 in vitro. Methods BxPC3 cells were treated with cyclopamine, YH16 or bination 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 bined 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. bined with YH16 resulted in greater growth inhibition than used alone (). Both cyclopamine and YH16 induced apoptosis of BxPC3 cells. Furthermore, bination of the two drugs led to a higher apoptosis rate (). Cyclopamine or YH16 alone downregulated Bcl2 expression and upregulated Bax expression at the mRNA level. bination of the two drugs could enhance the inhibitory effect significantly (). Conclusion Cyclopamine and YH16 can inhibit the proliferation of BxPC
3 cells and lead to their apoptosis. Moreover, bined with YH16 increases the inhibitory effect, which might be related to the regulation of apoptosisrelated proteins Bcl2 and Bax.
KEY WORDS: Cyclopamine; YH16; pancreatic cancer; cell proliferation; apoptosis
Hedgehog(HH)信号通路是一个高度保守的调控胚胎发育的信号通路,参与了胰腺、胃、结肠等消