title: β-elemene sensitizes hepatocellular carcinoma cells to oxaliplatin by preventing oxaliplatin-induced degradation of copper transporter 1.
abstract: β-elemene, a Curcuma wenyujin plant extract, has been used widely as a tumor adjuvant therapeutic agent. However, how to obtain optimum therapeutic effects by combining this compound with other agents remain unclear. In this study, we found that β-elemene, which alone had little effect on hepatocellular carcinoma (HCC) cell proliferation, exerted a synergistic anti-proliferative effect in HCC cells when dosed in combination with oxaliplatin, which increased the amounts of platinum accumulation and platinum-DNA adduct significantly and augmented the oxaliplatin-induced apoptosis. Western blot and laser scanning confocal microscopy studies indicated that β-elemene enhanced the sensitivity of HCC cells to oxaliplatin by upregulating copper transporter 1 (CTR1), a major controller of intracellular platinum accumulation. In an orthotopic transplantation HCC model in nude mice, HCC tumor growth was inhibited significantly by oxaliplatin combined with β-elemene, as compared with oxaliplatin alone. Notably, CTR1 protein expression in xenograft HCC was upregulated in mice who received β-elemene treatment. Taken together, our findings show that β-elemene can block the reduction of CTR1 resulting from oxaliplatin treatment, and therefore has a synergistic anti-HCC effect with oxaliplatin by enhancing cellular uptake of oxaliplatin. The synergistic effects of β-elemene and oxaliplatin deserve further evaluation in clinical settings.
authors: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai 200032, P.R.China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, P.R.China.
authors: Xiaoqiang
authors: X
authors: Li
authors: Department of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
authors: Zhenhai
authors: Z
authors: Lin
authors: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai 200032, P.R.China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, P.R.China.
authors: Bo
authors: B
authors: Zhang
authors: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai 200032, P.R.China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, P.R.China.
authors: Lei
authors: L
authors: Guo
authors: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai 200032, P.R.China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, P.R.China.
authors: Shuang
authors: S
authors: Liu
authors: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai 200032, P.R.China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, P.R.China.
authors: Hui
authors: H
authors: Li
authors: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai 200032, P.R.China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, P.R.China.
authors: Jubo
authors: J
authors: Zhang
authors: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai 200032, P.R.China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, P.R.China.
authors: Qinghai
authors: Q
authors: Ye
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D000079923:Copper Transporter 1; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D059748:Proteolysis / Q000187:drug effects*; D012717:Sesquiterpenes / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; D009363:Neoplasm Proteins; D009944:Organoplatinum Compounds; C490079:SLC31A1 protein, human; D012717:Sesquiterpenes; C445979:beta-elemene; D000077150:Oxaliplatin