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

2017; Impact Journals LLC; Volume: 8; Issue: 14 Linguagem: Inglês

10.18632/oncotarget.15575

1949-2553

Yang Cheng, Rong-Cheng Luo, Hang Zheng, Biao Wang, Yahui Liu, DingLi Liu, JinZhang Chen, Wanfu Xu, Aimin Li, Yun Zhu,

Liver physiology and pathology

// Yang Cheng 1, 2 , RongCheng Luo 3 , Hang Zheng 4 , Biao Wang 5 , YaHui Liu 3 , DingLi Liu 6 , JinZhang Chen 6 , WanFu Xu 1, 2 , AiMin Li 3 , Yun Zhu 6 1 Digestive Department, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, China 2 Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, China 3 Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, Guangdong 510315, China 4 Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China 5 Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China 6 Liver Tumor Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China Correspondence to: Yun Zhu, email: zyfreemail@126.com AiMin Li, email: liaim2005@yahoo.com 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.