Ye Qi-Fa, Zhang Yi-Chuan, Peng Xiao-Qing, Long Zhi, Ming Ying-Zi, He Le-Ye
Engineering and Technology Research Center for Transplantation Medicine of the National Ministry of Health, Hunan, China.
Asian Pac J Cancer Prev. 2012;13(6):2485-9. doi: 10.7314/apjcp.2012.13.6.2485.
Notch is an important signaling pathway that regulates cell fate, stem cell maintenance and the initiation of differentiation in many tissues. It has been reported that activation of Notch-1 contributes to tumorigenesis. However, whether Notch signaling might have a role in chemoresistance of prostate cancer is unclear. This study aimed to investigate the effects of Notch-1 silencing on the sensitivity of prostate cancer cells to docetaxel treatment.
siRNA against Notch-1 was transfected into PC-3 prostate cancer cells. Proliferation, apoptosis and cell cycle distribution were examined in the presence or absence of docetaxel by MTT and flow cytometry. Expression of p21(waf1/cip1) and Akt as well as activation of Akt in PC-3 cells were detected by Western blot and Real-time PCR.
Silencing of Notch-1 promoted docetaxel induced cell growth inhibition, apoptosis and cell cycle arrest in PC-3 cells. In addition, these effects were associated with increased p21(waf1/cip1) expression and decreased Akt expression and activation in PC-3 cells.
Notch-1 promotes chemoresistance of prostate cancer and could be a potential therapeutic target.
Notch是一种重要的信号通路，可调节细胞命运、干细胞维持以及许多组织中分化的起始。据报道，Notch-1的激活有助于肿瘤发生。然而，Notch信号通路是否在前列腺癌的化疗耐药中发挥作用尚不清楚。本研究旨在探讨Notch-1沉默对前列腺癌细胞对多西他赛治疗敏感性的影响。
将针对Notch-1的小干扰RNA（siRNA）转染至PC-3前列腺癌细胞中。通过MTT法和流式细胞术在有或无多西他赛的情况下检测细胞增殖、凋亡和细胞周期分布。通过蛋白质免疫印迹法和实时聚合酶链反应检测PC-3细胞中p21（waf1/cip1）和Akt的表达以及Akt的激活情况。
Notch-1沉默促进了多西他赛诱导的PC-3细胞生长抑制、凋亡和细胞周期阻滞。此外，这些效应与PC-3细胞中p21（waf1/cip1）表达增加、Akt表达和激活降低有关。
Notch-1促进前列腺癌的化疗耐药，可能是一个潜在的治疗靶点。
