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J Vet Sci 2017; 18(4): 419-429  https://doi.org/10.4142/jvs.2017.18.4.419
Inhibitory effects of resveratrol on hepatitis B virus X protein-induced hepatocellular carcinoma
Seungmo Park1,2, Jihae Lim3, Jong Rhan Kim4, Seongbeom Cho1,*
1BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, 2Institute of Laboratory Animal Resources, 3College of Pharmacy, and 4Advanced Institutes of Convergence Technology, Seoul National University, Seoul 08826, Korea
Correspondence to: Seongbeom Cho
Tel/Fax: +82-2-880-1270; E-mail: chose@snu.ac.kr
Received: September 1, 2016; Revised: January 11, 2017; Accepted: February 7, 2017; Published online: December 31, 2017.
Abstract
Liver cancer occurs very frequently worldwide and hepatocellular carcinoma (HCC) accounts for more than 80% of total primary liver cancer cases. In this study, the anticarcinogenic effects of resveratrol against hepatitis B virus (HBV)-induced HCC were investigated by using HBV X-protein-overexpressing Huh7 (Huh7-HBx) human hepatoma cells. MTT assay showed that resveratrol decreased cell viability. Fluorescence-activated cell-sorter analysis showed that resveratrol induced G1 cell cycle arrest without increasing the sub-G1 phase cell population. Therefore, we evaluated its effect on regulation of cyclin D1, which is critically involved in G1/S transition. Resveratrol lowered cyclin D1 transcription. Western blot analysis of the effects of resveratrol on upstream cyclin D1 transcriptional signaling, extracellular signal-related kinase (ERK), p90RSK, Akt, and p70S6K revealed inhibition of Akt but not the ERK signaling pathway. Collectively, the results indicate that resveratrol inhibits Huh7-HBx proliferation by decreasing cyclin D1 expression through blockade of Akt signaling. We investigated the anticarcinogenic effect and mechanism of resveratrol in xenograft model mice implanted with Huh7-HBx cells. Intraperitoneal resveratrol injection reduced tumor size in the mice. Expression of survivin was reduced, but cyclin D1 was not affected. The results demonstrate that resveratrol treatment may help manage HBV-induced HCC by regulating survivin.
Keywords: Akt pathway, hepatitis B virus X protein, hepatocellular carcinoma, resveratrol, survivin


© 2017 The Korean Society of Veterinary Science.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.