Department of Pharmacy, 159411The Third People's Hospital of Chengdu, Chengdu, Sichuan, People's Republic of China.
Wuya College of Innovation, 58575Shenyang Pharmaceutical University, Shenyang, Liaoning, People's Republic of China.
Hum Exp Toxicol. 2021 Dec;40(12):2048-2062. doi: 10.1177/09603271211017609. Epub 2021 May 31.
The mechanism of cytotoxicity of silibinin on two human hepatocellular carcinoma (HCC) cell lines, HepG2 (p53 wild-type) and Hep3B cells (p53 null), is examined in relation with the induction of autophagy and phosphorylation of AMP-activated protein kinase (p-AMPK).
Levels of apoptosis in relation to the levels of autophagy and those of glycolysis-related proteins, glucose transporter 1/4 (Glut1/4) and hexokinase-II (HK2), in HepG2 and Hep3B cells were examined.
Silibinin-induced apoptosis was incomplete for HCC cell death in that up-regulated autophagy and/or reduced level of glycolysis, which are induced by silibinin treatment, antagonized silibinin-induced apoptosis. Inhibition of autophagy with 3-methyl adenine (3MA) or blocking of AMP-activated protein kinase (AMPK) activation with Compound C (CC) enhanced silibinin-induced apoptosis. The results confirm that AMPK involved in autophagy as well as in glycolysis remaining with silibinin is responsible for attenuation of silibinin-induced apoptosis. Blocking of AMPK or autophagy contributes to the enhancement of silibinin's cytotoxicity to HepG2 and Hep3B cells.
This study shows that incomplete apoptosis of HCC by silibinin treatment becomes complete by repression of autophagy and/or glycolysis.
研究水飞蓟宾对两种人肝癌（HCC）细胞系 HepG2（野生型 p53）和 Hep3B 细胞（p53 缺失）的细胞毒性作用的机制，与自噬的诱导和 AMP 激活蛋白激酶（p-AMPK）的磷酸化有关。
检测 HepG2 和 Hep3B 细胞中与自噬和糖酵解相关蛋白（葡萄糖转运蛋白 1/4（Glut1/4）和己糖激酶-II（HK2））水平相关的细胞凋亡水平。
水飞蓟宾诱导的肝癌细胞凋亡不完全，因为水飞蓟宾处理诱导的自噬上调和/或糖酵解水平降低拮抗了水飞蓟宾诱导的细胞凋亡。用 3-甲基腺嘌呤（3MA）抑制自噬或用化合物 C（CC）阻断 AMP 激活蛋白激酶（AMPK）的激活增强了水飞蓟宾诱导的细胞凋亡。结果证实，AMPK 参与自噬和糖酵解的活性，与水飞蓟宾一起负责减弱水飞蓟宾诱导的细胞凋亡。阻断 AMPK 或自噬有助于增强水飞蓟宾对 HepG2 和 Hep3B 细胞的细胞毒性。
本研究表明，水飞蓟宾治疗不完全的肝癌细胞凋亡通过抑制自噬和/或糖酵解变得完全。
