Inhibition of autophagy signiﬁcantly enhances combination therapy with sorafenib and HDAC inhibitors for human hepatoma cells

doi:10.3748/wjg.v20.i17.4953

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May 7, 2014 (publication date) through Apr 19, 2024

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. May 7, 2014; 20(17): 4953-4962
Published online May 7, 2014. doi: 10.3748/wjg.v20.i17.4953

Inhibition of autophagy signiﬁcantly enhances combination therapy with sorafenib and HDAC inhibitors for human hepatoma cells

Hang Yuan, Ai-Jun Li, Sen-Lin Ma, Long-Jiu Cui, Bin Wu, Lei Yin, Meng-Chao Wu

Hang Yuan, Ai-Jun Li, Sen-Lin Ma, Long-Jiu Cui, Bin Wu, Lei Yin, Meng-Chao Wu, Department of the 2^nd Special Treatment, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China

Author contributions: Yuan H, Li AJ and Ma SL performed the majority of the experiments; Cui LJ, Wu B and Yin L provided vital reagents and analytical tools and were involved in editing the manuscript; Li AJ and Wu MC coordinated and provided the collection of human materials and provided financial support for this work; Yuan H and Li AJ designed the study and wrote the manuscript.

Supported by Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University

Correspondence to: Ai-Jun Li, MD, Department of the 2^nd Special Treatment, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No. 225, Changhai Road, Shanghai 200438, China. ajli62@gmail.com

Telephone: +86-21-81875531 Fax: +86-21-81875531

Received: August 25, 2013
Revised: December 4, 2013
Accepted: January 2, 2014
Published online: May 7, 2014

Core Tip

Core tip: In this study, we investigated the antiproliferative effect of sorafenib in combination with the histone deacetylase inhibitor vorinostatin in human hepatoma cell lines (Hep3B, HepG2, and PLC/PRF/5). We also examined whether the combination therapy was enhanced by the inhibition of autophagy. Our results showed that the combination of vorinostat with sorafenib synergistically reduced cell proliferation in hepatocellular carcinoma cells by inducing apoptosis and cell cycle arrest. Synergistic changes in cell cycle and cell survival regulators were also observed.