P-0070 Curcumin Inhibit the Epithelial–Mesenchymal Transition Induced by Hypoxia in Hepatocellular Carcinoma Cell Line HEPG2 in Vitro

Abstract

IntroductionHepatocellular carcinoma is one of the most lethal cancers in the worlds due to the aggressive biological characteristics of the tumor. A critical event in the early stage of invasion and metastasis of tumor is the epithelial–mesenchymal transition. Evidences revealed that hypoxia could induce the epithelial–mesenchymal transition via the up-regulation of the hypoxia-inducible factor-1&agr; (HIF-1&agr;) and increase the invasion and metastasis of tumor cells ultimately. This study is aimed to investigate the effect of Curcumin, the principle active ingredient in turmeric which is derived from the rhizome of Curcuma longa, on epithelial–mesenchymal transition in hepatocellular cancer cell line HepG2 under the hypoxia condition induced by cobalt chloride (CoCl2). MethodsHepG2 cells were divided to 3 groups: normal control group, CoCl2 (10 µmol/L) group, and CoCl2 plus Curcumin (10 µmol/L) group. After 48h of treatment, proliferation of cell was determined with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The invasion of HepG2 was detected by Transwell invasion assay. The mRNA expression of HIF-1&agr; was determined by real-time RT-PCR. The proteins of HIF-1&agr;, E-cadherin and vimentin were determined by Western blotting. ResultsCompared with the normal control group, the proliferation of HepG2 cell in CoCl2 group was significantly increased and in CoCl2 plus Curcumin group was decreased. Furthermore, the invasion of HepG2 cells were inhibited significantly by Curcumin compared with CoCl2 group. The difference of mRNA expressions of HIF-1&agr; was not observed. Meanwhile, HIF-1&agr; was obviously up-regulated, E-cadherin was increased and vimentin was deceased at protein levels in hypoxia induced by CoCl2 which is abolished by Curcumin. ConclusionCurcumin abolished the up-regulation of proliferation and migration of HepG2 cell in hypoxia which induced by CoCl2, through decreased the expression of HIF-1&agr; protein, and inhibited the epithelial–mesenchymal transition of HepG2.