表观遗传学与卵巢癌耐药的关系研究

摘要

卵巢癌在妇科恶性肿瘤中致死率最高,目前其临床治疗手段主要是手术切除和辅助性化疗,但治疗后其易复发、易转移和易耐药的特性,使得很多抗肿瘤药对其作用仅限于初期治疗.研究表明肿瘤的发生、发展及其耐药机制与表观遗传学关系密切,而相关研究也证实卵巢癌的发生发展与耐药受表观遗传学的调控,如DNA甲基化,包括Ras相关区域1A基因(RASSF1A)和乳腺癌易感基因1(BRCA1)异常甲基化;组蛋白修饰,包括甲基化、乙酰化、磷酸化、泛素化等多种方式;微小RNA(miRNA)调控相关基因等.同时研究表明通过调控表观遗传学如DNA甲基转移酶抑制剂、组蛋白去乙酰化酶抑制剂等与传统抗肿瘤药物进行联合治疗能够显著提高卵巢癌的疗效,因此研究表观遗传学与卵巢癌的耐药机制有望为临床治疗卵巢癌提供新的思路与研究基础.%Ovarian cancer mortality in the gynecology malignant tumor is the highest,the main clinical treatment is surgical resection and adjuvant chemotherapy,but easy to relapse after treatment.The research shows that the occurrence and development of tumor and drug resistance are related to epigenetics.The related researches also confirmed that epigenetics regulated the occurrence and development of ovarian cancer and drug resistance,such as DNA methylation,including RA SSF1A abnormal methylation and BRCA 1 abnormal methylation,histone modification including the methylation,acetylation,phosphorylation,ubiquitin,and so on,and miRNA genes.The epigenetics such as DNA methyltransferase inhibitors or histone deacetylase inhibitors can significantly improve the curative effect of ovarian cancer.The study of epigenetics and drug resistance in ovarian cancer are expected to provide new ideas and basis for clinical treatment of ovarian cancer.