Department of Geriatric Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8675, Japan.
Cancer Lett. 2013 Oct 1;339(1):116-27. doi: 10.1016/j.canlet.2013.07.015. Epub 2013 Jul 20.
The present study is the first to demonstrate the synergetic effect of statins (atorvastatin and simvastatin) and gamma-tocotrienol (γ-T3) on human malignant mesothelioma (MM). Statin + γ-T3 combinations induced greater cell growth inhibition more than each single treatment via inhibition of mevalonate pathway, a well-known target of both γ-T3 and statins. γ-T3 was necessary for endoplasmic reticulum stress markers CHOP and GRP78, whereas an intrinsic apoptotic marker, caspase 3 activation was induced only in the presence of statins. Overall, the combination of γ-T3 and statins could be useful for MM therapy and functions in a complementary style.
本研究首次证明了他汀类药物（阿托伐他汀和辛伐他汀）和γ-生育三烯酚（γ-T3）对人恶性间皮瘤（MM）的协同作用。他汀类药物+γ-T3 联合治疗通过抑制甲羟戊酸途径（γ-T3 和他汀类药物的共同靶点），比单一治疗诱导更大的细胞生长抑制作用。γ-T3 对于内质网应激标记物 CHOP 和 GRP78 是必需的，而内在凋亡标记物 caspase 3 的激活仅在存在他汀类药物的情况下诱导。总的来说，γ-T3 和他汀类药物的联合应用可能对 MM 的治疗有用，并以互补的方式发挥作用。
