Bai Shoumin, Chen Ting, Yu Xiaoli, Luo Ming, Chen Xianju, Lin Chunhao, Lai Yiming, Huang Hai
Department of Radiation Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P.R. China.
Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P.R. China.
Oncol Rep. 2017 May;37(5):2819-2828. doi: 10.3892/or.2017.5510. Epub 2017 Mar 16.
Matrine, a Sophora alkaloid, exhibits antiproliferative and anti-carcinogenic activities through several mechanisms. In a previous study, we found that matrine could effectively inhibit the proliferation of castration-resistant prostate cancer (CRPC). In the present study, the effect of matrine and LY294002 on the expression of the Akt/FoxO3a signaling pathway was examined by western blot analyses and RT-PCR. We discovered that matrine significantly inhibited the proliferation of both prostate cancer cell line PC-3 and prostate epithelial cell line RWPE1, induced apoptosis and induced cell cycle arrest. In addition, LY294002 was found to enhance the effect of matrine. Furthermore, the effects of matrine on the inhibition of proliferation and the induction of cell cycle arrest and cell apoptosis were more effective on PC-3 than on RWPE1 cells. Compared to RWPE1 cells, matrine exerted a more powerful influence on PC-3 cells in increasing the expression of the relevant protein. Our data suggested that FoxO3a-Bim and FoxO3a-P27 may mediate matrine-inhibited proliferation of CRPC cells by activating cell apoptosis and inducing cell cycle arrest. Matrine exhibited high selectivity in killing CRPC cells. Our findings demonstrated that matrine could be used in a potential therapeutic role in the management of CRPC in humans.
苦参碱是一种苦参生物碱，通过多种机制发挥抗增殖和抗癌活性。在先前的一项研究中，我们发现苦参碱可有效抑制去势抵抗性前列腺癌（CRPC）的增殖。在本研究中，通过蛋白质印迹分析和逆转录聚合酶链反应（RT-PCR）检测了苦参碱和LY294002对Akt/FoxO3a信号通路表达的影响。我们发现，苦参碱显著抑制前列腺癌细胞系PC-3和前列腺上皮细胞系RWPE1的增殖，诱导细胞凋亡并导致细胞周期停滞。此外，发现LY294002可增强苦参碱的作用。此外，苦参碱对增殖的抑制以及对细胞周期停滞和细胞凋亡的诱导作用在PC-3细胞上比在RWPE1细胞上更有效。与RWPE1细胞相比，苦参碱对PC-3细胞中相关蛋白表达的增加影响更大。我们的数据表明，FoxO3a-Bim和FoxO3a-P27可能通过激活细胞凋亡和诱导细胞周期停滞来介导苦参碱对CRPC细胞增殖的抑制作用。苦参碱在杀死CRPC细胞方面表现出高选择性。我们的研究结果表明，苦参碱可用于人类CRPC治疗的潜在用途。
