关键词: &gamma, -丁基甜菜碱双加氧酶, 维甲酸X受体, 肝癌, 肉碱合成

Abstract: To study the gene expression of γ-butyrobetainedioxygenase (γ-BBD) in primary hepatocellular carcinoma and the effect of retinoic acid on the expression of γ-BBD in rat hepatoma cells.A DEN-induced primary hepatocellular carcinoma model was established in vivo and a rat hepatoma cells (RH-35 cells) was treated with 1 μmol/L 13-cis-retinoic acid (13-cis-RA) in vitro.In DEN-induced primary hepatocellular carcinoma model,the Sprague Dawley rats received intraperitoneal injections of diethylnitrosamine (DEN) at 50 mg/kg body weight once a week.The expression levels ofγ-BBD and retinoid x receptor gamma (RXRγ) were measured by western blotting and real-time PCR in DEN-induced primary hepatocellular carcinoma and RH-35 cells treated with 13-cis-RA,respectively.The cell cycle of RH-35 cells treated with retinoic acid was analyzed by flow cytometry.Compared with those of control group,the mRNA abundance and protein expression levels of γ-BBD and RXRγwere significantly low in DEN-induced primary hepatocellular carcinoma.However,compared with those of control group,the mRNA abundance and protein expression levels of γ-BBD and RXRγwere significantly high in RH-35 cells which were treated with retinoic acid for 48 hours.Furthermore,RH-35 cells treated with retinoic acid for 48 hours were significantly arrested in G1 phase.These results indicated that the expression levels of γ-BBD and RXRγwere significantly down-regulated in DEN-induced primary hepatocellular carcinoma,and that the 13-cis-RA could induce and up-regulate the expression of RXRγ and γ-BBD in RH-35 cells.This suggests that the effect of 13-cis-RA on the expression of γ-BBD may promote the synthesis of carnitine in rat hepatocellular carcinoma cells.

Key words: retinoic acid, &gamma, -butyrobetainedioxygenase, retinoid x receptors, hepatocarcinoma, carnitine biosynthesis