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Research Paper|Volume 12, Issue 12|pp 11717—11731

Resveratrol inhibits the malignant progression of hepatocellular carcinoma via MARCH1-induced regulation of PTEN/AKT signaling

Hanhan Dai1, Minjing Li3, Wei Yang1, Xiucui Sun1, Peiyuan Wang1, Xia Wang4, Jiaqi Su1, Xu Wang1, Xuemei Hu2, Mingdong Zhao1
  • 1Department of Imaging, Binzhou Medical University, Yantai 264003, Shandong, PR China
  • 2Department of Immunology, Binzhou Medical University, Yantai 264003, Shandong, PR China
  • 3Department of Chinese medicine prescription, Binzhou Medical University, Yantai 264003, Shandong, PR China
  • 4Department of Oral Pathology, Binzhou Medical University, Yantai 264003, Shandong, PR China
* Equal contribution
Received: November 10, 2019Accepted: May 18, 2020Published: June 12, 2020
https://doi.org/10.18632/aging.103338

Copyright © 2020 Dai et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Resveratrol is a common, naturally occurring polyphenol confirmed with inhibited the cellular effects of carcinogenesis. However, the molecular mechanism underlying resveratrol’s action against hepatocellular carcinoma (HCC) is still unclear. In addition, MARCH1 promotes the initiation and progression of HCC, but it is unclear whether resveratrol exerts antitumor efforts by regulating MARCH1 expression. This study determined the molecular mechanisms underlying the antitumor effects of resveratrol in HCC. Resveratrol induced apoptosis and inhibited the proliferation, migration, and invasion of HCC cell lines (HepG2 and Hep3B). In addition, it inhibited MARCH1 and phospho–protein kinase B (p-AKT) expression but upregulated the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) dose-dependently both in vitro and in vivo. MARCH1 knockdown by small interfering RNA (siRNA) also increased PTEN expression. Meanwhile, MK2206 (an AKT inhibitor) and bisperoxovanadium (BPV; a PTEN inhibitor) combined with resveratrol decreased MARCH1 expression more than the single-treatment HCC group. These results suggested that resveratrol affects the biological characteristics of HCC via downregulation of MARCH1 expression.