期刊
ONCOTARGET
卷 8, 期 14, 页码 23265-23276出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.15575
关键词
sorafenib; fluvastatin; hepatocellular carcinoma; TLR4; SDF-1 alpha
资金
- Postdoctoral Research Funding of Guangzhou Women and Children's Medical Center [5001-2150172]
- Guangdong Natural Science Foundation [2016A030310254]
- China Postdoctoral Science Foundation [2016M600648]
- National Natural Science Foundation [81602646]
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-kappa B pathways via Toll-like receptor 4 in HCC cells. Combined treatment also inhibited expression of stromal cell-derived factor 1 alpha 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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