Center for Drug Safety Evaluation and Research of Zhejiang University, Hangzhou, China; Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Pharmazie. 2021 Oct 1;76(10):511-514. doi: 10.1691/ph.2021.1646.
The lack of effective strategies remains a pivotal challenge for hepatocellular carcinoma (HCC) treatment. YAP/ TAZ is a promising target for effective drugs against HCC. In this study, we profiled the regulatory effect of 98 drugs on transcriptional activity of YAP/TAZ and identified the calcimimetic agent cinacalcet as a potent YAP inhibitor. Cinacalcet inhibited YAP expression in HCC models at both transcriptional and protein levels, and ultimately arrested cell proliferation of HCC. Overexpression of YAP weakened the anticancer efficacy of cinacalcet, indicating that YAP was responsible for the antineoplastic activity of cinacalcet. Collectively, this study suggested cinacalcet as a feasible anticancer drug for HCC via its inhibition on YAP/TAZ.
缺乏有效的策略仍然是肝细胞癌 (HCC) 治疗的一个关键挑战。YAP/TAZ 是针对 HCC 的有效药物的一个有前途的靶点。在这项研究中，我们对 98 种药物对 YAP/TAZ 转录活性的调节作用进行了分析，并确定钙敏感受体激动剂西那卡塞是一种有效的 YAP 抑制剂。西那卡塞在 HCC 模型中在转录和蛋白水平上抑制 YAP 的表达，并最终阻止 HCC 的细胞增殖。YAP 的过表达削弱了西那卡塞的抗癌疗效，表明 YAP 是西那卡塞抗肿瘤活性的原因。总的来说，这项研究表明西那卡塞通过抑制 YAP/TAZ 成为 HCC 可行的抗癌药物。
