蒽环类抗生素是常用的肿瘤化疗药物。使用蒽环类抗生素可引起处于免疫控制状态的慢性HBV感染者、甚至既往感染者的HBV再激活，但其机制尚未充分阐明。调节因子RFX1是一种DNA损伤效应蛋白，参与DNA损伤修复。研究表明，RFX1可与HBV 增强子I区的EP位点和核心启动子区的类EP位点结合，反式激活HBV转录，进而促进HBV复制。我们的前期研究发现，蒽环类抗生素的代表性药物阿霉素及其衍生物表阿霉素在体外不仅促进HBV复制，还能上调RFX1表达，且二者变化趋势一致。但将HBV增强子I区的EP位点突变后，阿霉素对HBV复制水平的促进作用明显减弱。据此推测，蒽环类抗生素可通过上调RFX1表达，增强HBV增强子I的转录活性，进而促进HBV复制。本课题将探索蒽环类抗生素通过RFX1引起肿瘤患者HBV再激活的新机制，为靶向预防肿瘤化疗过程中HBV再激活、提高肿瘤疗效提供依据。

Hepatitis B virus (HBV) reactivation is well documented in previously resolved or inactive HBV carriers who receive cancer chemotherapy. With increasing life expectancy and the global increasing in cancer, chemotherapy induced reactivation of hepatitis B is likely to become an increasing problem. Anthracycline antibiotics is one of the most common chemotherapy drugs inducing HBV reactivation. However, the exact mechanism of HBV reactivation induced by anthracycline antibiotics is not fully understood. Regulatory factor X-box 1 (RFX1) is one of the DNA damage effectors, and takes part in the repair of DNA damage. Meanwhile, RFX1 is one of the most important transcription factors which transactivate HBV transcription and promote HBV replication through the EP site in HBV enhancer I region and the analogue of EP site in HBV core promoter region. Our previous research found that doxorubicin and epirubicin could promote HBV replication and RFX1 expression in parallel, but for HBV with EP site mutation, the effect is much weaker. We hypothesized that anthracycline antibiotics may enhance the transcription activity of HBV enhancer I and core promoter through promoting RFX1 expression, and then promote HBV replication. In this study, we will investigate the influence of anthracycline antibiotics on the transcription activity of HBV enhancer I and core promoter, verify that RFX1 takes part in the regulation of HBV replication by anthracycline antibiotics, and then elucidate the new mechanism of anthracycline antibiotics upregulating HBV transcription and replication. The present study will identify a novel DNA damage-HBV replication pathway in liver cancer cell, which may be a potential target for prevention in HBV reactivation and efficacy in tumor therapy.