Curcumin enhances temsirolimus-induced apoptosis in human renal carcinoma cells through upregulation of YAP/p53
Curcumin enhances temsirolimus-induced apoptosis in human renal carcinoma cells through upregulation of YAP/p53
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姜黄素通过上调 YAP/p53 增强替西罗莫司诱导的人肾癌细胞凋亡
DOI：
10.3892/ol.2016.5376
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发表时间：
2016-11
期刊：
影响因子：
2.9
通讯作者：
Guo Peng
中科院分区：
文献类型：
--
作者：
Xu Shan;Yang Zheng;Fan Yizeng;Guan Bing;Jia Ding;Gao Yang;Wang Ke;Wu Kaijie;Wang Xinyang;Zheng Pengsheng;He Dalin;Guo Peng
姜黄素经常被用作治疗各种类型疾病的治疗剂，并且已知可增强细胞的药物敏感性。在本研究中，姜黄素和替西罗莫司处理对人肾细胞癌（RCC）细胞凋亡的联合作用进行了研究。替西罗莫司是雷帕霉素信号通路机制靶点的抑制剂，用于转移性RCC的一线治疗。结果表明，姜黄素与替西罗莫司组合显著诱导RCC细胞凋亡，然而，单独使用姜黄素或替西罗莫司处理后未观察到这种效果。与替西罗莫司和姜黄素的共同治疗导致裂解的聚ADP-核糖聚合酶和半胱天冬酶3的激活，p53表达和核转位的上调，以及B细胞淋巴瘤2蛋白表达的下调。此外，姜黄素处理被证明以时间依赖的方式增加了Yes相关蛋白（雅普）的表达，这与姜黄素诱导的p53表达模式在2小时后同时发生。此外，小干扰RNA敲低雅普导致RCC细胞中姜黄素诱导的p53表达增加的减弱。总之，目前的结果表明，姜黄素和替西罗莫司联合治疗通过激活p53对人RCC细胞的凋亡具有协同作用。从机制上讲，雅普在姜黄素诱导p53表达中是必需的。此外，结果表明，用低浓度姜黄素预处理或共处理细胞增强了对靶向药物的反应，这为克服人类RCC中的耐药性提供了一种潜在的新颖且有效的策略。
Curcumin has frequently been used as a therapeutic agent in the treatment of various types of disease and is known to enhance the drug sensitivity of cells. In the present study, the combined effect of curcumin and temsirolimus treatment on apoptosis in human renal cell carcinoma (RCC) cells was investigated. Temsirolimus is an inhibitor of the mechanistic target of rapamycin signaling pathway and used in the first-line treatment of metastatic RCC. It was demonstrated that curcumin combined with temsirolimus markedly induced apoptosis in RCC cells, however this effect was not observed following curcumin or temsirolimus treatment alone. Co-treatment with temsirolimus and curcumin led to the activation of cleaved poly ADP-ribose polymerase and caspase 3, upregulation of p53 expression and nuclear translocation, and downregulation of B-cell lymphoma 2 protein expression. Furthermore, curcumin treatment was demonstrated to increase Yes-associated protein (YAP) expression in a time-dependent manner, which was concurrent with the curcumin-induced expression pattern of p53 after 2 h. In addition, knockdown of YAP by small interfering RNA caused the attenuation of curcumin-induced increased p53 expression in RCC cells. In conclusion, the present results indicate that combined curcumin and temsirolimus treatment has a synergistic effect on apoptosis in human RCC cells, through the activation of p53. Mechanistically, YAP is essential in the induction of p53 expression by curcumin. Furthermore, the results suggest that pre-treatment or co-treatment of cells with low concentration curcumin enhances the response to targeted drugs, and this presents a potentially novel and efficient strategy to overcome drug resistance in human RCC.
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DOI：
--
发表时间：
2010-12
期刊：
Minerva urologica e nefrologica = The Italian journal of urology and nephrology
影响因子：
--
作者：
H. Gerullis;T. Ecke;Christoph Eimer;Heuck Cj;T. Otto
通讯作者：
H. Gerullis;T. Ecke;Christoph Eimer;Heuck Cj;T. Otto
姜黄素：通过调节分子途径预防癌症的潜在候选者。
影响因子：
--
作者：
Rahmani AH;Al Zohairy MA;Aly SM;Khan MA
通讯作者：
Khan MA
影响因子：
3.8
作者：
K. Rashid;P. Sil
通讯作者：
K. Rashid;P. Sil
影响因子：
4.8
作者：
Zhou, Xiaoguang;Tolstov, Yanis;Arslan, Aysenur;Roth, Wilfried;Gruellich, Carsten;Pahernik, Sascha;Hohenfellner, Markus;Duensing, Stefan
通讯作者：
Duensing, Stefan
姜黄素通过下调膀胱癌细胞中的 YAP/TAZ 促进 KLF5 蛋白酶体降解
影响因子：
5.6
作者：
Gao Y;Shi Q;Xu S;Du C;Liang L;Wu K;Wang K;Wang X;Chang LS;He D;Guo P
通讯作者：
Guo P