mTOR抑制剂雷帕霉素的抗肿瘤作用

Anti-tumor effect of mTOR inhibitor rapamycin

哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)是参与生命活动的多条信号通路的下游因子,其中就包括PI3K/Akt/mTOR信号通路,在细胞生长、分化、转移和存活中地位显著,已成为癌症治疗的一个重要靶标。第一代m TOR抑制剂雷帕霉素(RAPA)最初作为一种新型的免疫抑制药物在器官移植领域应用广泛。随着对该药物及m TOR信号通路的深入研究,人们慢慢地认识到RAPA除免疫抑制外还具有诱导肿瘤细胞凋亡、阻断细胞周期、抑制信号传导、影响基因转录水平及其对表观遗传学的调控作用。本文主要综述了近年来雷帕霉素在抗肿瘤方面的研究进展,同时讨论了雷帕霉素抗肿瘤的局限性。

The mammalian target of rapamycin(mTOR) is a downstream factor of multiple signaling pathways involved in life activities, including the PI3K/Akt/mTOR signaling pathway. It plays a significant role in cell growth, differentiation, metastasis and survival. It has become an important target for cancer therapy. The first generation of the mTOR inhibitor, rapamycin(RAPA), was initially used as a new type of immunosuppressive drug in organ transplantation. With the further study of RAPA and m TOR signaling pathway, it is gradually recognized that in addition to the immunosuppression ability, RAPA has the abilities to induce tumor cell apoptosis, block cell cycle, inhibit signal transduction, affect gene transcription level, and regulate the epigenetics surroundings. This article mainly reviews the recent advances in anti-tumor research of rapamycin, and discusses the limitations of rapamycin against tumors.