人肝肿瘤细胞中霉酚酸Ⅱ相代谢特征研究

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

目的:研究和比较体内外肝肿瘤细胞和正常肝细胞Ⅱ相代谢特征。方法:采用体外培养人肝肿瘤细胞株与正常人肝细胞株、临床来源肝肿瘤组织与肿瘤旁组织,检测UGT1A9的基因与蛋白水平表达,以霉酚酸为模型药物、HPLC法定量测定霉酚酸及其葡萄糖醛酸结合物,考察霉酚酸在上述细胞和组织微粒体中的代谢强弱,分析肝肿瘤细胞与正常肝细胞中II相代谢酶UGT1A9的功能与差异。结果:体外培养人肝肿瘤细胞HepG2和临床来源人肝细胞瘤组织中UGT1A9表达分别高于正常人肝细胞L-O2和人肝肿瘤癌旁组织,差异具有统计学意义(P<0.01)。然而人肝肿瘤细胞HepG2和人肝肿瘤组织对霉酚酸的代谢能力远低于人正常肝细胞L-O2和人肝肿瘤癌旁组织(P<0.05)。结论:人肝肿瘤细胞与临床来源人肝细胞瘤组织中UGT1A9的表达与功能存在不相关性,提示肿瘤细胞中虽然UGT1A9表达较高,但其功能存在某些缺失,可能与肿瘤细胞内营养相对缺乏有关。

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 UGTIA9 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 incu- bation of mycophenolic acid with clinically ob- tained human hepatic carcinoma tissue and adja- cent tissues was also performed. RESULTS： The expression of UGTIA9 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 metabo- lism of mycophenolic acid in HepG2 and human liver tumor tissue was much lower than in L-O2 and human liver paraneoplastic tissues. CON- CLUSION： UGT1A9 expression and function are not consistent in HepG2 and human hepatoma tissues, which suggesting that although UGTIA9 expression is higher in tumor cells, but with some deficiency in function. This may be associated with a lack of nutrition in tumor.