靶向抑制肠道菌β-葡萄糖醛酸苷酶在肿瘤预防和治疗中的应用  

Applications of BGUSs inhibition in tumor prevention and chemotherapy

作　　者：吴蓉蓉 陈智强 贾翼菲 陈宏绮 王盼盼 燕茹[1] WU Rongrong;CHEN Zhiqiang;JIA Yifei;CHEN Hongqi;WANG Panpan;YAN Ru(State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Science(ICMS),University of Macao,Macao 999078,China)

机构地区：[1]澳门大学中华医药研究院暨中药质量研究国家重点实验室,中国澳门

出　　处：《中国临床药理学与治疗学》2021年第8期964-974,共11页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：澳门科技发展基金(FDCT0098/2019/A2);广东省自然科学基金面上项目(2019A1515012195);澳门大学科研基金(MYRG2018-00091-ICMS)。

摘　　要：肠道菌β-葡萄糖醛酸苷酶(BGUSs)是肠道菌群产生的一类重要水解酶,其通过水解内源性和外源性葡萄糖醛酸苷影响肿瘤发生发展以及化疗药物的疗效(药效/毒性)。近年来,越来越多的研究尝试通过抑制肠道BGUSs降低患癌风险和减轻化疗药物引起的毒副作用。但由于BGUSs具有基因和结构的多样性、生理病理功能的复杂性以及对特定抑制剂响应的差异性,表征介导特定疾病或药物不良反应的BGUSs并发展有效的选择性抑制剂面临巨大的挑战。本文概述了BGUSs的结构和功能的最新进展,汇总了近年来在BGUSs介导的致癌物和肿瘤化疗药物代谢方面的发现、BGUSs抑制剂的研发及其预防肿瘤和缓解化疗药物不良反应的临床前研究结果,并讨论了将抑制BGUSs作为肿瘤预防和药物治疗新策略的前景。Bacterialβ-glucuronidases(BGUSs)are an important type of hydrolase produced by gut microbiota and play an important role in tumor development and chemotherapy by deconjugating a large number of endogenous and exogenous glucuronides.In recent years,BGUSs inhibition has emerged as a promising approach to reduce cancer risk and alleviate gastrointestinal toxicity of chemotherapy drugs.However,a growing body of evidence underlines great genetic and structural diversity,functional promiscuity,and varied inhibition propensity of BGUSs,which have posed enormous challenges to identifying BGUSs involved in a specific pathophysiological or pharmacological process and developing effective inhibitors.In this review,we summarize the latest advances in structure and function of BGUSs and review the findings of BGUSs-mediated carcinogen reactivation and deconjugation of chemotherapy drugs in recent years,as well as the discovery of BGUSs inhibitors and preclinical investigation of their applications in cancer prevention and drug therapy.Finally,we discuss the prospects of BGUSs inhibition as a new strategy for tumor prevention and drug therapy.

关 键 词：Β-葡萄糖醛酸苷酶 肠道菌群 癌症风险 化疗 

分 类 号：R969.1[医药卫生—药理学]