人肝肿瘤细胞中霉酚酸II相代谢特征研究

中国临床药理学与治疗学 ›› 2013, Vol. 18 ›› Issue (9): 961-968.

• 基础研究 • 下一篇

人肝肿瘤细胞中霉酚酸II相代谢特征研究

顾融融¹, 姜超², 张峰³, 刘福坤², 肖文璟¹, 曹蓓¹, 石建¹, 葛纯¹, 阿基业¹, 王广基¹

¹中国药科大学药物代谢与动力学重点实验室;
²江苏省中医院消化肿瘤外科;
³江苏省人民医院普外科,南京 210009,江苏

收稿日期:2013-03-02 修回日期:2013-08-10 发布日期:2013-09-07
通讯作者: 阿基业,男,研究员,硕士生导师,研究方向:药物代谢动力学、代谢组学。Tel: 025-83271192 E-mail: jiye_2005@yahoo.com.cn
作者简介:顾融融,女,硕士研究生,研究方向:药物代谢动力学、代谢组学。Tel: 025-83271192 E-mail: rrgoo89@126.com
基金资助:
江苏省自然科学基金项目 (BK2012762);国家自然科学基金项目(81072692)

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

GU Rong-rong¹, JIANG Chao², ZHANG feng³, LIU Fu-kun², XIAO Wen-jing¹, CAO Bei¹, SHI Jian¹, GE Chun¹, A Ji-ye¹, WANG Guang-Ji¹

¹Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University;
²Surgical Department of Digestion Oncology, Jiangsu Province Hospital of TCM;
³Jiangsu Province Hospital, General Surgery Department, Nanjing 210009, Jiangsu, China

Received:2013-03-02 Revised:2013-08-10 Published:2013-09-07

摘要/Abstract

摘要： 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。

关键词: HepG₂, L-O2, UGT1A9, 霉酚酸

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

中图分类号:

R969. 2

顾融融, 姜超, 张峰, 刘福坤, 肖文璟, 曹蓓, 石建, 葛纯, 阿基业, 王广基. 人肝肿瘤细胞中霉酚酸II相代谢特征研究[J]. 中国临床药理学与治疗学, 2013, 18(9): 961-968.

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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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

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