Grape Seed Proanthocyanidins Induce Autophagy and Modulate Survivin in HepG2 Cells and Inhibit Xenograft Tumor Growth in Vivo

葡萄籽原花青素诱导 HepG2 细胞自噬、调节 Survivin 并抑制体内异种移植肿瘤生长

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作者:Lihua Wang, Weidong Huang, Jicheng Zhan

Abstract

Liver cancer is one of the leading causes of death worldwide. Although radiotherapy and chemotherapy are effective in general, they present various side effects, significantly limiting the curative effect. Increasing evidence has shown that the dietary intake of phytochemicals plays an essential role in the chemoprevention or chemotherapy of tumors. In this work, HepG2 cells and nude mice with HepG2-derived xenografts were treated with grape seed proanthocyanidins (GSPs). The results showed that GSPs induced autophagy, and inhibition of autophagy increased apoptosis in HepG2 cells. In addition, GSPs also reduced the expression of survivin. Moreover, survivin was involved in GSPs-induced apoptosis. GSPs at 100 mg/kg and 200 mg/kg significantly inhibited the growth of HepG2 cells in nude mice without causing observable toxicity and autophagy, while inducing the phosphorylation of mitogen-activated protein kinase (MAPK) pathway-associated proteins, p-JNK, p-ERK and p-p38 MAPK and reducing the expression of survivin. These results suggested that GSPs might be promising phytochemicals against liver cancer.

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