Phase II metabolism characteristics of Mycophenolic acid in the human liver tumor cells

Abstract

Abstract: AIM: To assess the differences in the II phase combination capacity of the tumor cell lines and normal cell lines, we study the metabolic capacity of HepG₂ and L-O2 as for mycophenolic acid, as well as the expression of UGT1A9 in two cell lines.METHODS: Tumor cells were treated with 2.5 mmol/L and 1 mmol/L mycophenolic acid (UGT1A9 substrate) with normal cells of the corresponding organ as the control group. HPLC was used to determine the levels of drug and the glucuronidation metabolite intracellular and extracellular. Microsomal incubation of mycophenolic acid with clinically obtained human hepatic carcinoma tissue and adjacent tissues was also performed.RESULTS: The expression of UGT1A9 in HepG₂ and human liver tumor tissue was much higher than in L-O2 and adjacent tissues with a significant difference respectively (P<0.01). However, the metabolism of mycophenolic acid in HepG₂ and human liver tumor tissue was much lower than in L-O2 and human liver paraneoplastic tissues.CONCLUSION: UGT1A9 expression and function are not consistent in HepG₂ and human hepatoma tissues, which suggesting that although UGT1A9 expression is higher in tumor cells, but with some deficiency in function. This may be associated with a lack of nutrition in tumor.

Key words: HepG₂, L-O2, UGT1A9, Mycophenolic

CLC Number:

R969. 2

GU Rong-rong, JIANG Chao, ZHANG feng, LIU Fu-kun, XIAO Wen-jing, CAO Bei, SHI Jian, GE Chun, A Ji-ye, WANG Guang-Ji. Phase II metabolism characteristics of Mycophenolic acid in the human liver tumor cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(9): 961-968.

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