Borahay Mostafa A, Kilic Gokhan S, Yallampalli Chandrasekha, Snyder Russell R, Hankins Gary D V, Al-Hendy Ayman, Boehning Darren
From the Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas 77555, the Department of Biochemistry and Molecular Biology, University of Texas Health Sciences Center at Houston, Houston, Texas 77030,
From the Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas 77555.
J Biol Chem. 2014 Dec 19;289(51):35075-86. doi: 10.1074/jbc.M114.583575. Epub 2014 Oct 30.
Statins are drugs commonly used for the treatment of high plasma cholesterol levels. Beyond these well known lipid-lowering properties, they possess broad-reaching effects in vivo, including antitumor effects. Statins inhibit the growth of multiple tumors. However, the mechanisms remain incompletely understood. Here we show that simvastatin inhibits the proliferation of human leiomyoma cells. This was associated with decreased mitogen-activated protein kinase signaling and multiple changes in cell cycle progression. Simvastatin potently stimulated leiomyoma cell apoptosis in a manner mechanistically dependent upon apoptotic calcium release from voltage-gated calcium channels. Therefore, simvastatin possesses antitumor effects that are dependent upon the apoptotic calcium release machinery.
他汀类药物是常用于治疗高血浆胆固醇水平的药物。除了这些广为人知的降脂特性外，它们在体内还具有广泛的作用，包括抗肿瘤作用。他汀类药物可抑制多种肿瘤的生长。然而，其机制仍未完全了解。在此我们表明，辛伐他汀可抑制人平滑肌瘤细胞的增殖。这与丝裂原活化蛋白激酶信号传导的降低以及细胞周期进程的多种变化有关。辛伐他汀以一种机械性地依赖于电压门控钙通道释放凋亡钙的方式，有力地刺激了平滑肌瘤细胞凋亡。因此，辛伐他汀具有依赖于凋亡钙释放机制的抗肿瘤作用。
