靶向沉默 TRPM7 离子通道可诱导胰腺腺癌细胞复制性衰老，并增强吉西他滨的细胞毒性。
Targeted silencing of TRPM7 ion channel induces replicative senescence and produces enhanced cytotoxicity with gemcitabine in pancreatic adenocarcinoma.
机构信息
Division of Hematology-Oncology, Department of Medicine, Penn State College of Medicine, Pennsylvania State University, 500 University Drive, Hershey, PA 17033, USA.
出版信息
Cancer Lett. 2012 May 1;318(1):99-105. doi: 10.1016/j.canlet.2011.12.007. Epub 2011 Dec 11.
Abstract
The transient receptor potential TRPM7 ion channel is required for cellular proliferation in pancreatic epithelia and adenocarcinoma. To elucidate the mechanism that mediates the function of TRPM7, we examined its role in survival of pancreatic cancer cells. RNA interference-mediated silencing of TRPM7 did not induce apoptotic cell death. TRPM7-deficient cells underwent replicative senescence with up-regulation of p16(CDKN2A) and WRN mRNA. The combination of anti-TRPM7 siRNA and gemcitabine produced enhanced cytotoxicity as compared to gemcitabine alone. Thus, TRPM7 is required for preventing senescence, and modulation of TRPM7 expression may help improve treatment response of pancreatic cancer by combining with apoptosis-inducing agents.
摘要
瞬时受体电位 TRPM7 离子通道对于胰腺上皮和腺癌中的细胞增殖是必需的。为了阐明介导 TRPM7 功能的机制，我们研究了它在胰腺癌细胞存活中的作用。RNA 干扰介导的 TRPM7 沉默不会诱导细胞凋亡。TRPM7 缺陷细胞经历复制性衰老，p16(CDKN2A)和WRN mRNA 上调。与单独使用吉西他滨相比，抗 TRPM7 siRNA 和吉西他滨的组合产生了增强的细胞毒性。因此，TRPM7 对于防止衰老是必需的，并且调节 TRPM7 的表达可能有助于通过与诱导凋亡的药物联合使用来改善胰腺癌的治疗反应。
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