Nrf2激动剂干预肿瘤化疗药物毒性的研究进展

Progress of researches on Nrf2 activators in intervention of tumor chemotherapy toxicities

化疗是肿瘤治疗中最重要的手段之一,但其疗效和应用受限于肿瘤组织的耐药性及对正常组织的毒性。红系衍生的核因子2相关因子2(nuclear factor erythroid-derived 2-related factor 2,Nrf2)是调控细胞抗氧化响应和药物代谢的核心转录因子,当前针对其在肿瘤预防和放化疗耐受中的作用已有大量研究。然而,关于Nrf2在化疗药物对正常组织毒性中的作用和机制研究尚不够深入,其临床相关性有待进一步探究。本文将就Nrf2在常见化疗药物毒性中的作用进行综述,并重点讨论萝卜硫素、富马酸二甲酯和甲基巴多索隆等3种典型的Nrf2激动剂在干预肿瘤化疗药物常见毒性中的作用、机制以及可能的应用前景,以期促进对Nrf2在肿瘤化疗中作用的全面理解,并为今后相关的肿瘤化疗辅助用药的开发和临床应用提供理论依据。

Chemotherapy is one of the most important tumor therapies,but its efficacy and clinical applications are limited by chemoresistance of tumors and toxicities to normal tissues.Nuclear factor erythroid-derived 2-related factor 2(Nrf2)is a pivotal transcription factor that regulates cellular antioxidant response and drug metabolism,its roles in cancer chemoprevention and therapy resistance have been extensively investigated.However,the involvement of Nrf2 in chemotherapy toxicity remains to be explored,and its clinical significance deserves further investigation.In the present article,we will briefly review the known roles of Nrf2 in common toxicities of chemotherapy drugs,and summarize the application of sulforaphane,dimethyl fumarate and bardoxolone methyl in the intervention of chemotherapy toxicities.This review is expected to enhance a comprehensive understanding of the roles and mechanisms of Nrf2 in tumor chemotherapy,and to provide scientific rationale for the development and clinical application of chemotherapy-associated complementary and alternative drugs.