DNA甲基化与卵巢癌耐药关系的研究进展

Advances in Research of Relationship between DNA Methylation and Drug Resistance in Ovarian Cancer

卵巢癌为女性常见的恶性肿瘤之一,其恶性程度高,预后差。目前卵巢癌患者的化疗策略是基于铂类和紫杉醇的组合。虽然大多数卵巢癌患者对化疗敏感,但仍有许多初始反应者最终发展为化疗耐药。以往的研究认为癌基因激活、抑癌基因失活主要是基因突变、缺失导致的DNA序列改变。而现有研究表明许多肿瘤的重要基因并未发生突变、缺失,基因表达的异常主要通过DNA甲基化实现,且DNA甲基化和其他表观遗传修饰可能是可逆的。这就使得表观遗传因子成为疾病预防和对化疗药物重获敏感性的候选者。大量研究也证实,在耐药和敏感卵巢癌细胞中DNA甲基化水平差异表达。亦有研究使用DNA甲基化酶抑制剂抑制DNA甲基化,以期达到逆转卵巢癌细胞耐药的目的。现综述DNA甲基化与卵巢癌耐药之间的关系。

Ovarian cancer is one of the common malignant tumors in women,with high malignancy and poor prognosis.The current chemotherapy strategy for treating ovarian cancer patients is based on a combination of platinum and paclitaxel.Although most ovarian cancer patients are sensitive to chemotherapy,many initial responders eventually develop chemotherapy resistance.Previous studies have suggested that oncogene activation and tumor suppressor gene inactivation are mainly DNA sequence changes caused by gene mutations and deletions.However,existing studies have shown that many important tumor genes are not mutated or deleted.Gene expression abnormalities are mainly achieved by DNA methylation,DNA methylation and other epigenetic modifications may be reversible.This makes epigenetic factors a candidate for disease prevention and regaining sensitivity to chemotherapeutic drugs.Numerous studies have also confirmed differential expression of DNA methylation levels in drug-resistant and sensitive ovarian cancer cells.DNA methylase inhibitors have also been used to inhibit DNA methylation in order to reverse the resistance of ovarian cancer cells.The relationship between DNA methylation and ovarian cancer resistance is reviewed in this article.