Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, PR China; Experiment Center, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510700, PR China.
Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510260, PR China.
Eur J Pharmacol. 2018 Mar 15;823:58-64. doi: 10.1016/j.ejphar.2018.01.031. Epub 2018 Feb 4.
Aspirin not only reduces the incidence of hepatocellular carcinoma (HCC) but also plays a synergistic role with chemotherapy for HCC treatment. However, the underlying mechanisms remain incompletely elucidated. Given that autophagy triggers cancer cell death, the present study examined the autophagic effect of aspirin on HCC cells. Results showed that aspirin increased LC3II/LC3I ratio, decreased p62 expression, and enhanced autophagic flux (autophagosome and autolysosome puncta) in Hep3B, HepG2, or SMMC-7721 cells, reflecting the autophagy of HCC cells. The autophagic effects of aspirin depended on Beclin-1 expression. Aspirin disrupted the interaction between Bcl-2 and Beclin-1. In addition to activating the AMP-activated protein kinase, c-Jun N-terminal kinase, and Glycogen synthase kinase-3 pathways, aspirin inhibited the mammalian-target-of rapamycin-S6K1/4E-BP1 signaling. Aspirin induced autophagy of HCC cell. This study contributes to understanding the chemoprotective and inhibitory effects of aspirin on HCC development.
阿司匹林不仅降低肝细胞癌（HCC）的发生率，而且还与 HCC 的化学疗法治疗发挥协同作用。然而，其潜在机制仍不完全清楚。鉴于自噬可引发癌细胞死亡，本研究检测了阿司匹林对 HCC 细胞的自噬作用。结果表明，阿司匹林可增加 Hep3B、HepG2 或 SMMC-7721 细胞中 LC3II/LC3I 比值、降低 p62 表达、并增强自噬流（自噬体和自溶酶体斑点），这反映了 HCC 细胞的自噬作用。阿司匹林的自噬作用取决于 Beclin-1 的表达。阿司匹林破坏了 Bcl-2 和 Beclin-1 之间的相互作用。除了激活 AMP 激活的蛋白激酶、c-Jun N 末端激酶和糖原合成酶激酶-3 通路外，阿司匹林还抑制了哺乳动物雷帕霉素靶蛋白-S6K1/4E-BP1 信号。阿司匹林诱导 HCC 细胞自噬。本研究有助于理解阿司匹林对 HCC 发展的化学预防和抑制作用。
