Department of Gynecology and Obstetrics, Tongji hospital, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
Department of Gynecology and Obstetrics, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450015, Henan Province, China.
Virology. 2018 Aug;521:118-128. doi: 10.1016/j.virol.2018.05.026. Epub 2018 Jun 12.
Adenovirus E1B 55-kilodalton (E1B-55K) mediated DAXX degradation represents a potential mechanism by which E1B-55K sensitizes cancer cells to chemotherapy. Here we report the effects of E1B-55K-mediated DAXX degradation in chemoresistant ovarian cancer cells on response to chemotherapy. Cells with E1B-55K expression were more sensitive to cisplatin than cells without E1B-55K expression. In vivo C13* xenograft studies showed that the combination of cisplatin and E1B-55K was markedly more effective to slow tumor growth and to confer prolonged survival of tumor-bearing mice than either cisplatin or E1B-55K alone. Our studies show that DAXX plays an important role in cisplatin resistance in ovarian cancer, and strategies that promote DAXX degradation such as E1B-55K expression in combination with cisplatin can overcome drug resistance and improve responses to standard chemotherapy. These results also indicate that E1B-55K might be a novel agent for enhancing treatment responses for cisplatin-resistant ovarian cancer.
腺病毒 E1B 55kDa（E1B-55K）介导的 DAXX 降解代表了 E1B-55K 使癌细胞对化疗敏感的潜在机制。在这里，我们报告了 E1B-55K 介导的 DAXX 降解在化疗耐药卵巢癌细胞对化疗反应中的作用。表达 E1B-55K 的细胞对顺铂比不表达 E1B-55K 的细胞更敏感。体内 C13*异种移植研究表明，顺铂和 E1B-55K 的联合应用比单独使用顺铂或 E1B-55K 更能显著减缓肿瘤生长并延长荷瘤小鼠的生存时间。我们的研究表明，DAXX 在卵巢癌对顺铂的耐药性中起重要作用，而促进 DAXX 降解的策略，如 E1B-55K 的表达与顺铂联合应用，可能克服耐药性并提高对标准化疗的反应。这些结果还表明，E1B-55K 可能是一种增强顺铂耐药性卵巢癌治疗反应的新型药物。
