NATURAL PRODUCT RESEARCH AND DEVELOPMENT ›› 2019, Vol. 31 ›› Issue (10): 1791-1798. doi: 10.16333/j.1001-6880.2019.10.018

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The effects of retinoic acid on the expression of γ-butyrobetaine dioxygenase and carnitine biosynthesis in rat hepatocellular carcinoma cells

QU Shang-lan1,2#,REN Wei-wei1,2#,SONG Liu-dong2,FENG Wei-yang1*   

  1. 1School of Basic Medical Sciences,Kunming Medical University;2School of Pharmaceutical Science &Yunnan Key Laboratory of Pharmacology for Natural Products,Kunming Medical University,Kunming 650500,China
  • Online:2019-10-28 Published:2019-11-11

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

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