GADD45A与肿瘤治疗  

GADD45A and Tumor Therapy

作　　者：胡晓红 杨力芳[2] 李丹[1] HU Xiao-hong;YANG Li-fang;LI Dan(College of Biology,Hunan University,Changsha 410082,Hunan,China;Cancer Research Institute,Central South University,Changsha 410008,Hunan,China)

机构地区：[1]湖南大学生物学院,中国湖南长沙410082 [2]中南大学肿瘤研究所,中国湖南长沙410008

出　　处：《生命科学研究》2021年第2期124-130,共7页Life Science Research

摘　　要：生长阻滞和DNA损伤基因45A(growth arrest and DNA damage-inducible 45A,GADD45A)是第1个被发现的由P53激活的应激诱导基因,同时也是P63、P73、BRCA1及MYC的靶标基因。GADD45A作为DNA损伤修复基因,受P53依赖(电离辐射诱导)和独立于P53(紫外线诱导)的途径调节,参与DNA损伤修复、细胞周期阻滞、凋亡、自噬、血管形成等生物学功能,与肿瘤发生发展密切相关。在大多数肿瘤的治疗中,化疗药物直接或者间接(如脱甲基化、乙酰化)上调其表达水平,提高癌细胞药物敏感性;同时,在放射治疗过程,过表达GADD45A可干预放射抵抗。然而,在少数肿瘤的治疗中,GADD45A的表达反而能够提高癌细胞的存活率。本文主要对GADD45A在肿瘤治疗中所发挥的作用及机制进行综述。Growth arrest and DNA damage-inducible 45A(GADD45A)is the first P53 activated stress-induced gene,which is also a target gene of P63,P73,BRCA1 and MYC.As a DNA damage repair gene,GADD45A is regulated by P53 dependent(induced by ionizing radiation)and P53 independent(induced by ultraviolet light)pathways,and participates in DNA damage repair,cell cycle arrest,apoptosis,autophagy,angiogenesis and other biological functions,which are closely related to tumorigenesis and tumor development.In the treatment of most tumors,chemotherapeutics directly or indirectly(e.g.demethylation and acetylation)upregulates GADD45A expression and improves the drug sensitivity of cancer cells.Meanwhile,overexpression of GADD45A can interfere with radiation resistance during radiotherapy.However,for a few tumors,the expression of GADD45A can increase the survival rate of cancer cells.Here the roles and mechanism of GADD45A in tumor therapy are mainly reviewed.

关 键 词：生长阻滞和DNA损伤基因45A(GADD45A) 肿瘤治疗 凋亡 细胞周期阻滞 细胞耐药 放疗敏感 

分 类 号：Q71[生物学—分子生物学] R730.58[医药卫生—肿瘤]