葫芦素 I 通过 ERK-mTOR-STAT3 信号通路诱导 A549 细胞发生促死亡自噬。
Cucurbitacin I induces pro-death autophagy in A549 cells via the ERK-mTOR-STAT3 signaling pathway.
机构信息
Research Core Facility, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.
Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.
出版信息
J Cell Biochem. 2018 Jul;119(7):6104-6112. doi: 10.1002/jcb.26808. Epub 2018 Mar 25.
Natural products are a great source of cancer chemotherapeutic agents. In the present study, the anticancer effects of cucurbitacin I on A549 cells were investigated. Cucurbitacin I decreased cell viability, inhibited colony formation, and induced apoptosis in A549 cells. Cucurbitacin I caused accumulation of autophagosome and dose-dependent expression of LC3II protein. Autophagy inhibitors 3-methyladenine (3-MA) inhibited autophagy induced by cucurbitacin I and relieved cucurbitacin I-triggered cell death and apoptosis in A549 Cells. Cucurbitacin I treatment inhibits the ERK activation and the downstream phosphorylation level of mTOR and STAT3, but not the PI3K/Akt pathway. Furthermore, treatment with the mTOR activator MHY-1485, which also suppressed cucurbitacin I-induced LC3II expression, and also reversed cucurbitacin I-induced cell death and apoptosis. Taken together, these results suggest that cucurbitacin I induced pro-death autophagy through ERK/mTOR/STAT3 signaling cascade in A549 cells.
天然产物是癌症化疗药物的重要来源。本研究探讨了葫芦素 I 对 A549 细胞的抗癌作用。葫芦素 I 降低细胞活力，抑制集落形成，并诱导 A549 细胞凋亡。葫芦素 I 导致自噬体积累，并呈剂量依赖性表达 LC3II 蛋白。自噬抑制剂 3-甲基腺嘌呤 (3-MA) 抑制葫芦素 I 诱导的自噬，并减轻 A549 细胞中葫芦素 I 触发的细胞死亡和凋亡。葫芦素 I 处理抑制 ERK 激活和 mTOR 和 STAT3 的下游磷酸化水平，但不抑制 PI3K/Akt 通路。此外，用 mTOR 激活剂 MHY-1485 处理，也抑制了葫芦素 I 诱导的 LC3II 表达，并逆转了葫芦素 I 诱导的细胞死亡和凋亡。综上所述，这些结果表明葫芦素 I 通过 ERK/mTOR/STAT3 信号级联诱导 A549 细胞中的促死亡自噬。
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