Oncotarget

Research Papers:

Synergistic anti-tumor efficacy of sorafenib and fluvastatin in hepatocellular carcinoma

Yang Cheng, Rong Cheng Luo, Hang Zheng, Biao Wang, YaHui Liu, Ding Li Liu, JinZhang Chen, WanFu Xu, AiMin Li and Yun Zhu _

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Oncotarget. 2017; 8:23265-23276. https://doi.org/10.18632/oncotarget.15575

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Abstract

Yang Cheng1,2, RongCheng Luo3, Hang Zheng4, Biao Wang5, YaHui Liu3, DingLi Liu6, JinZhang Chen6, WanFu Xu1,2, AiMin Li3, Yun Zhu6

1Digestive Department, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, China

2Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, China

3Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, Guangdong 510315, China

4Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China

5Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China

6Liver Tumor Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China

Correspondence to:

Yun Zhu, email: [email protected]

AiMin Li, email: [email protected]

Keywords: sorafenib, fluvastatin, hepatocellular carcinoma, TLR4, SDF-1α

Received: November 09, 2016     Accepted: February 13, 2017     Published: February 21, 2017

ABSTRACT

Drug resistance to sorafenib is common in patients with hepatocellular carcinoma(HCC). We examined the effects of a combination of sorafenib and fluvastatin on HCC using in vitro and in vivo models. The dual treatment induced apoptosis and reduced cellular viability in HCC more effectively than either drug alone. The combination treatment also inhibited activation of hepatic stellate cells, whereas single drug treatments did not. On a molecular level, combined treatment inhibited activation of the MAPK and NF-κB pathways via Toll-like receptor 4 in HCC cells. Combined treatment also inhibited expression of stromal cell-derived factor 1α in HCC cells, which further inhibited the MAPK pathway in hepatic stellate cells. These results suggest that a combination of sorafenib and fluvastatin may be a promising therapeutic strategy for patients with advanced HCC.


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