Autophagy induction by silibinin positively contributes to its anti-metastatic capacity via AMPK/mTOR pathway in renal cell carcinoma.
Autophagy induction by silibinin positively contributes to its anti-metastatic capacity via AMPK/mTOR pathway in renal cell carcinoma.
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DOI：
10.3390/ijms16048415
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发表时间：
2015-04-15
影响因子：
5.6
通讯作者：
Zeng J
中科院分区：
文献类型：
--
作者：
Li F;Ma Z;Guan Z;Chen Y;Wu K;Guo P;Wang X;He D;Zeng J
水飞蓟宾是一种来自奶蓟种子的膳食癌症化学预防类黄酮，据报道对肾细胞癌（RCC）具有抗转移作用，但这种现象的机制尚未完全清楚。本研究旨在探讨自噬在调节水飞蓟宾诱导的肾癌细胞抗转移效应中的潜在作用。以RCC ACHN和786-O细胞为模型，发现水飞蓟宾处理后，自噬溶酶体空泡形成，LC 3-II的表达增加，并产生点状荧光模式，其中单体红色荧光蛋白增强的绿色荧光蛋白-LC 3（mRFP-EGFP-LC 3）蛋白均为细胞自噬的标志物。自噬通量诱导水飞蓟宾在RCC细胞，由LC 3周转测定。从机制上讲，5 '-一磷酸腺苷激活蛋白激酶（AMPK）/哺乳动物雷帕霉素靶蛋白（mTOR）途径被确定参与调节水飞蓟宾诱导的自噬。此外，自噬诱导被证明积极有助于水飞蓟宾诱导的抗转移作用的RCC细胞在体外。自噬的激活增强了水飞蓟宾对肾癌细胞迁移和侵袭的抑制作用，而抑制自噬则减弱了这种抑制作用，这为水飞蓟宾诱导的自噬与肾癌转移抑制之间的潜在联系提供了新的信息，自噬的诱导可能为今后肾癌转移的治疗策略提供了新的思路。
Silibinin, a dietary cancer chemopreventive flavonoid from the seeds of milk thistle, has been reported to exhibit anti-metastatic effects on renal cell carcinoma (RCC), but the mechanism underlying this phenomenon is not fully understood. The present study aimed at examining the potential role of autophagy in regulating silibinin-induced anti-metastatic effects on RCC cells. Using RCC ACHN and 786-O cells as a model system in vitro, we found that silibinin treatment increased the expression of LC3-II, resulted in the formation of autophagolysosome vacuoles, and caused a punctate fluorescence pattern with the monomeric red fluorescence protein-enhanced green fluorescence protein-LC3 (mRFP-EGFP-LC3) protein, which all are markers for cellular autophagy. Autophagy flux was induced by silibinin in RCC cells, as determined by LC3 turnover assay. Mechanically, the adenosine 5'-monophosphate activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway was identified as involved in regulation of silibinin-induced autophagy. Furthermore, autophagy induction was demonstrated to positively contribute to silibinin-induced anti-metastatic effects on RCC cells in vitro. Activation of autophagy enhanced silibinin-induced inhibition of migration and invasion of RCC cells, while inhibition of autophagy attenuated it. These findings thus provide new information about the potential link between autophagy and metastasis inhibition induced by silibinin, and the induction of autophagy may shed some light into future treatment strategies for metastatic RCC.
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DOI：
10.1136/bmj.g4797
发表时间：
2014-11-10
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Jonasch E;Gao J;Rathmell WK
通讯作者：
Rathmell WK
影响因子：
9.7
作者：
Li, Lei;Gao, Ye;Sun, Yi
通讯作者：
Sun, Yi
水飞蓟宾通过抑制 EGFR/MMP-9 信号通路对 EGFR 信号诱导的肾细胞癌进展具有抑制作用
影响因子：
4.2
作者：
Liang, Liang;Li, Lei;He, Dalin
通讯作者：
He, Dalin
影响因子：
13.3
作者：
Raina, Komal;Agarwal, Chapla;Agarwal, Rajesh
通讯作者：
Agarwal, Rajesh
影响因子：
15.3
作者：
Bhatt, Jaimin R.;Finelli, Antonio
通讯作者：
Finelli, Antonio