Jin Hong-Guang, Wu Guo-Zhen, Wu Guo-Hua, Bao Yong-Ge
Department of Orthopedics, Affiliated Hospital of Inner Mongolia University for The Nationalities, Tongliao, Inner Mongolia 028007, P.R. China.
Department of Cardiology, Tongliao Traditional Chinese Medicine Hospital, Tongliao, Inner Mongolia 028000, P.R. China.
Oncol Lett. 2018 May;15(5):6257-6264. doi: 10.3892/ol.2018.8178. Epub 2018 Mar 5.
Rapamycin is known to inhibit the mammalian target of rapamycin complex (mTORC)1 signaling pathway, but it is unable to effectively inhibit mTORC2, resulting in activation of protein kinase B in multiple myeloma (MM) cell lines. Additionally, certain studies have suggested that resveratrol has an effect on human MM cells, and that rapamycin in combination with resveratrol may be useful in cancer therapy. The present study aimed to investigate the combined treatment effect of resveratrol and rapamycin on the MM MM1.S cell line. The results demonstrated that combined treatment with rapamycin and resveratrol effectively inhibited cell viability in the MM1.S cell line through inhibition of the mTORC1 and mTORC2 signaling pathways, compared with resveratrol or rapamycin monotherapy. In addition, cyclin D1 levels were decreased and the activation of caspase-3 and poly (ADP-ribose) polymerase was increased. These results suggested that downregulation of the mTOR signaling cascades is likely to be a crucial mediator in the impairment of viability and the induction of apoptosis resulting from combined therapy with resveratrol and rapamycin in MM1.S cells.
已知雷帕霉素可抑制哺乳动物雷帕霉素靶蛋白复合物（mTORC）1信号通路，但它无法有效抑制mTORC2，从而导致多发性骨髓瘤（MM）细胞系中的蛋白激酶B活化。此外，某些研究表明白藜芦醇对人MM细胞有作用，并且雷帕霉素与白藜芦醇联合使用可能对癌症治疗有用。本研究旨在探讨白藜芦醇和雷帕霉素联合治疗对MM细胞系MM1.S的效果。结果表明，与白藜芦醇或雷帕霉素单一疗法相比，雷帕霉素和白藜芦醇联合治疗通过抑制mTORC1和mTORC2信号通路有效抑制了MM1.S细胞系中的细胞活力。此外，细胞周期蛋白D1水平降低，半胱天冬酶-3和聚（ADP-核糖）聚合酶的活化增加。这些结果表明，mTOR信号级联的下调可能是白藜芦醇和雷帕霉素联合治疗导致MM1.S细胞活力受损和诱导凋亡的关键介质。
