自噬
安普克
SIRT3
癌症研究
白藜芦醇
转移
基因敲除
乳腺癌
癌细胞
化学
生物
细胞生物学
癌症
细胞凋亡
磷酸化
锡尔图因
蛋白激酶A
医学
内科学
药理学
乙酰化
生物化学
基因
作者
Jia Wang,Huang Ping,Xiafang Pan,Chunhua Xia,Hong Zhang,Han Zhao,Zhao Yuan,Jianming Liu,Chao Meng,Fanglan Liu
摘要
Abstract Resveratrol (Resv) has antitumorigenic and antimetastatic activities; however, the molecular mechanisms underlying the inhibitory effects of Resv on the invasion and metastasis of breast cancer cells are still a subject of debate. In our study, we demonstrated that Resv inhibited tumor cell proliferation and tumor growth. It also suppressed invasion and pulmonary metastasis of breast cancer by reversing the transforming growth factor beta 1 (TGF‐β1)‐mediated EMT process. Meanwhile, the anticarcinogenic effects of Resv were abolished by the autophagy blocker 3‐methyladenine (3‐MA) or Beclin 1 small interfering RNA. Moreover, Resv upregulated autophagy‐related genes and protein levels and induced the formation of autophagosomes in 4T1 breast cancer cells and xenograft mice, suggesting that autophagy was involved in the anticarcinogenic activities of Resv in both models. In addition, Resv‐induced autophagy by increasing the expression of SIRT3 and phosphorylated AMPK. SIRT3 knockdown reduced AMPK phosphorylation and autophagy‐related proteins levels, and suppressed the anticancer effects of Resv, demonstrating that the inhibitory effects of Resv on tumor progression were mediated via the SIRT3/AMPK/autophagy pathway. Taken together, our study provided novel insight into the anticancer effects of Resv and revealed that targeting the SIRT3/AMPK/autophagy pathway can serve as a new therapeutic target against breast cancer.
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