Andrographolide sensitizes prostate cancer cells to TRAIL-induced apoptosis

作     者：Ruo-Jing Wei Xin-Shi Zhang Da-Lin He 

作者机构：Department of Urology The First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061 China 

出 版 物：《Asian Journal of Andrology》 (亚洲男性学杂志（英文版）)

年 卷 期：2018年第20卷第2期

页      面：200-204页

核心收录：

学科分类：0710[理学-生物学] 083002[工学-环境工程] 0830[工学-环境科学与工程（可授工学、理学、农学学位）] 1002[医学-临床医学] 07[理学] 08[工学] 09[农学] 0903[农学-农业资源与环境] 071002[理学-动物学] 0713[理学-生态学] 

主　　题：andrographolide DR4 p53 reactive oxygen species tumor necrosis factor-related apoptosis-inducing ligand 

摘      要：Tumor necrosis factor-related apoptosis-inducing ligand （TRAIL） is a promising agent for anticancer therapy. The identification of small molecules that can establish the sensitivity of prostate cancer （PCa） cells to TRAIL-induced apoptosis is crucial for the targeted treatment of PCa. PC3, DU145, JAC-1, TsuPrl, and LNCaP cells were treated with Andrographolide （Andro） and TRAIL, and the apoptosis was measured using the Annexin V/PI double staining method. Real time-polymerase chain reaction （PCR） and Western blot analysis were performed to measure the expression levels of target molecules. RNA interference technique was used to down-regulate the expression of the target protein. We established a nude mouse xenograft model of PCa, which was used to measure the caspase-3 activity in the tumor cells using flow cytometry. In this research study, our results demonstrated that Andro preferentially increased the sensitivity of PCa cells to TRAIL-induced apoptosis at subtoxic concentrations, and the regulation mechanism was related to the up-regulation of DR4. In addition, it also increased the p53 expression and led to the generation of reactive oxygen species （ROS） in the cells. Further research revealed that the DR4 inhibition, p53 expression, and ROS generation can significantly reduce the apoptosis induced by the combination of TRAIL and Andro in PCa cells. In conclusion, Andro increases the sensitivity of PCa cells to TRAIL-induced apoptosis through the generation of ROS and up-regulation of p53 and then promotes PCa cell apoptosis associated with the activation of DR4.