葡萄糖氧化酶介导的抗癌疗法  

Anticancer therapy mediated by glucose oxidase

作　　者：何晓博 何咏竞 李鹏平 徐信 陈博[1] 曹国栋 熊茂明[1] HE Xiaobo;HE Yongjing;LI Pengping;XU Xin;CHEN Bo;CAO Guodong;XIONG Maoming(Department of General Surgery,First A liated Hospital of Anhui Medical University,Hefei 230022,Anhui Province,China;Department of Oncology Nutrition and Metabolism,Anhui Provincial Cancer Hospital,Hefei 230031,Anhui Province,China;Department of General Surgery,First People’s Hospital of Xiaoshan District,Hangzhou 311200,Zhejiang Province,China)

机构地区：[1]安徽医科大学第一附属医院普外科,安徽合肥230022 [2]安徽省肿瘤医院肿瘤营养与代谢科,安徽合肥230031 [3]杭州市萧山区第一人民医院普外科,浙江杭州311200

出　　处：《肿瘤》2020年第2期146-152,共7页Tumor

基　　金：国家自然科学基金资助项目(编号:81602425).

摘　　要：葡萄糖氧化酶是一种广泛存在于生物体内的内源性氧化还原酶。近年来,葡萄糖氧化酶因具有良好的生物相容性、低毒性以及对β-D-葡萄糖的催化作用等特性,在生物医学领域越来越引起人们的广泛关注。葡萄糖氧化酶能有效催化葡萄糖氧化成葡萄糖酸和过氧化氢,研究人员利用这一催化特性开发出了各种基于葡萄糖氧化酶的抗癌疗法:(1)葡萄糖消耗是癌症饥饿疗法的替代治疗策略;(2)氧气消耗增加肿瘤低氧,可用于肿瘤的低氧激活治疗;(3)葡萄糖酸生成可增加肿瘤微环境的酸性,从而触发pH响应性药物的释放;(4)过氧化氢的产生提高了肿瘤氧化应激水平,而且其暴露在光照环境(如近红外光照射下)或通过芬顿反应可以转化成有毒的羟基自由基,从而杀死癌细胞。除此之外,葡萄糖氧化酶还可以与其他生物酶、低氧激活前体药物、光敏剂或芬顿试剂联合应用,产生以饥饿疗法为主体,协同低氧激活疗法、氧化疗法、光动力疗法和光照疗法等的多模式协同抗癌疗法。本文首先介绍葡萄糖氧化酶介导的肿瘤单一疗法,然后系统性地阐述葡萄糖氧化酶介导的多模式协同抗癌疗法,以及多模式协同作用抗肿瘤的具体机制。Glucose oxidase is a kind of endogenous oxidoreductase which exists widely in organism.In recent years,due to its inherent biocompatibility,low toxicity and unique catalytic effect on betaD-glucose,glucose oxidase has attracted more and more attention in the field of biomedicine.Glucose oxidase can effectively catalyze the oxidation of glucose into gluconic acid and hydrogen peroxide.Researchers have developed various anticancer therapies based on glucose oxidase using this catalytic property:(1)glucose consumption provides alternative treatment strategies for cancer starvation;(2)oxygen consumption increases tumor hypoxia,which can be used for tumor hypoxia activation therapy;(3)the production of gluconic acid increases the acidity of tumor microenvironment,which can trigger the release of pH-responsive drugs;(4)the production of hydrogen peroxide increases the oxidative stress level of tumors.Hydrogen peroxide can be converted into toxic hydroxyl radicals by being exposed to light(such as near-infrared light)or fenton reaction,thus killing cancer cells.In addition,glucose oxidase can also be used in combination with other biological enzymes,hypoxia-activated prodrugs,photosensitizers or fenton reagents to produce the multi-mode synergistic anticancer therapies with starvation therapy as the main part,cooperating with hypoxia-activated therapy,oxidation therapy,photodynamic therapy and light therapy,etc.In this review,the glucose oxidase-mediated tumor monotherapy is firstly introduced,and the multi-mode synergistic anti-cancer therapy mediated by glucose oxidase as well as its specific anti-tumor mechanism are systematically elaborated.

关 键 词：肿瘤治疗方案 肿瘤微环境 低氧 葡萄糖氧化酶 饥饿疗法 协同疗法 

分 类 号：R730.5[医药卫生—肿瘤]