Yan Jiliang, Ma Chunyan, Cheng Jian, Li Zhengguo, Liu Chao
Department of Clinical Laboratory, Kaifeng Central Hospital, Kaifeng, Henan 475000, P.R. China.
Department of Oncology, Taishan Medical University Affiliated Zouping Hospital, Zouping, Shandong 256200, P.R. China.
Oncol Rep. 2015 Nov;34(5):2776-81. doi: 10.3892/or.2015.4202. Epub 2015 Aug 13.
HS1 associated protein X-1 (HAX-1), a substrate of Src family tyrosine kinases, plays a critical role in cell apoptosis. However, its functions in prostate cancer remains unclear. The present study explored the role and mechanism of HAX-1 in cancer cell apoptosis. The mRNA and protein levels of HAX-1 in the prostate cancer cell lines PC-3, VCaP and DU145 were assessed. Cell proliferation, apoptosis and caspase-9 activities were assessed in DU145 after HAX-1 siRNA treatment. The mRNA and protein levels of HAX-1 in prostate cancer cell lines PC-3, VCaP and DU145 were significantly higher than those in the primary prostate epithelial cells, and DU145 possess the highest mRNA and protein levels compared to PC-3 and VCaP. When HAX-1 was knocked down in DU145, cell proliferation was significantly decreased, accompanied by a decrease in Ki67 protein expression. Compared with the control and control siRNA groups, HAX-1 siRNA promoted cell apoptosis and caspase-9 activation in DU145. Furthermore, prostate cancer cells co-transfected with HAX-1 and caspase-9 promoted viability and reduced apoptosis. In contract, co-transfection of caspase-9 and HAX-1 siRNA suppressed the cell viability and enhanced apoptosis. In summary, the present study demonstrated that HAX-1 inhibits cell apoptosis through caspase-9 inactivation.
HS1相关蛋白X-1（HAX-1）是Src家族酪氨酸激酶的底物，在细胞凋亡中起关键作用。然而，其在前列腺癌中的功能仍不清楚。本研究探讨了HAX-1在癌细胞凋亡中的作用及机制。评估了前列腺癌细胞系PC-3、VCaP和DU145中HAX-1的mRNA和蛋白水平。在HAX-1 siRNA处理后的DU145细胞中评估细胞增殖、凋亡及半胱天冬酶-9活性。前列腺癌细胞系PC-3、VCaP和DU145中HAX-1的mRNA和蛋白水平显著高于原代前列腺上皮细胞，且与PC-3和VCaP相比，DU145的mRNA和蛋白水平最高。当DU145中的HAX-1被敲低时，细胞增殖显著降低，同时Ki67蛋白表达下降。与对照组和对照siRNA组相比，HAX-1 siRNA促进了DU145细胞的凋亡及半胱天冬酶-9的激活。此外，共转染HAX-1和半胱天冬酶-9的前列腺癌细胞活力增强且凋亡减少。相反，共转染半胱天冬酶-9和HAX-1 siRNA则抑制细胞活力并增强凋亡。总之，本研究表明HAX-1通过使半胱天冬酶-9失活来抑制细胞凋亡。
