Enhanced anticancer activity by the combination of vinpocetine and sorafenib via PI3K/AKT/GSK-3β signaling axis in hepatocellular carcinoma cells

被引：11

作者：

Zhang, Zuo-yan ^{[1
,2
]}

Dong, Shu-min ^{[1
,2
]}

Liu, Ye-han ^{[1
,2
]}

Zhang, Man-man ^{[1
,2
]}

Zhang, Jian-kang ^{[1
]}

Zhu, Hua-jian ^{[1
]}

Shao, Jia-an ^{[1
]}

Liu, Hua-qing ^{[1
]}

Li, Yang-ling ^{[3
]}

Zhang, Chong ^{[1
]}

Zeng, Ling-hui ^{[1
]}

机构：

[1] Zhejiang Univ City Coll, Sch Med, Dept Pharmacol, 51 Huzhou St, Hangzhou 310015, Zhejiang, Peoples R China

[2] Zhejiang Univ, Coll Pharmaceut Sci, Dept Pharmacol, Hangzhou, Zhejiang, Peoples R China

[3] Zhejiang Univ, Dept Clin Pharmacol, Key Lab Clin Canc Pharmacol & Toxicol Res Zhejian, Affiliated Hangzhou Peoples Hosp 1,Sch Med, Hangzhou, Zhejiang, Peoples R China

来源：

ANTI-CANCER DRUGS | 2021年 / 32卷 / 07期

关键词：

autophagy; combination; hepatocellular carcinoma; sorafenib; vinpocetine; GSK-3; beta; AUTOPHAGY; LIVER; INFLAMMATION; PATHWAY; RESISTANCE;

D O I：

10.1097/CAD.0000000000001056

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Vinpocetine is widely used to treat cerebrovascular diseases. However, the effect of vinpocetine to treat hepatocellular carcinoma (HCC) has not been investigated. In this study, we revealed that vinpocetine was associated with antiproliferative activity in HCC cells, but induced cytoprotective autophagy, which restricted its antitumor activity. Autophagy inhibitors improved the antiproliferative activity of vinpocetine in HCC cells. Sorafenib is effective to treat advanced HCC, but the effect of autophagy induced by sorafenib is indistinct. We demonstrated vinpocetine plus sorafenib suppressed the cytoprotective autophagy activated by vinpocetine in HCC cells and significantly induced apoptosis and suppressed cell proliferation in HCC cells. In addition, vinpocetine plus sorafenib activates glycogen synthase kinase 3 beta (GSK-3 beta) and subsequently inhibits cytoprotective autophagy induced by vinpocetine in HCC cells. Meanwhile, overexpression of GSK-3 beta was efficient to increase the apoptosis induced by vinpocetine plus sorafenib in HCC cells. Our study revealed that vinpocetine plus sorafenib could suppress the cytoprotective autophagy induced by vinpocetine and subsequently show synergistically anti-HCC activity via activating GSK-3 beta and the combination of vinpocetine and sorafenib might reverse sorafenib resistance via the PI3K/protein kinase B/GSK-3 beta signaling axis. Thus, vinpocetine may be a potential candidate for sorafenib sensitization and HCC treatment, and our results may help to elucidate more effective therapeutic options for HCC patients with sorafenib resistance. (C) 2021 Wolters Kluwer Health, Inc. All rights reserved.

引用

页码：727 / 733

页数：7

共 31 条

[11] Vinpocetine Suppresses Streptococcus pneumoniae-Induced Inflammation via Inhibition of ERK1 by CYLD [J].