Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, 210023, Nanjing, China.
Affiliated Drum Tower Hospital, Nanjing University School of Medicine, 210008, Nanjing, China.
Gene Ther. 2022 Aug;29(7-8):407-417. doi: 10.1038/s41434-020-00215-9. Epub 2021 Jan 7.
Camptothecin has been used in tumor therapy for a long time but its antitumor effect is rather limited due to the side effect and the drug resistance. FEN1, a major component of DNA repair systems, plays important roles in maintaining genomic stability via DNA replication and repair. Here we found that FEN1 inhibitor greatly sensitizes cancer cells to low-dose camptothecin. The combinative treatment of FEN1 inhibitor and 1 nM camptothecin induced a synthetic lethal effect, which synergistically suppressed cancer cell proliferation and significantly mediated apoptosis both in vitro and in vivo. Our study suggested that targeting FEN1 could be a potent strategy for tumor-targeting cancer therapy.
喜树碱长期以来一直被用于肿瘤治疗，但由于副作用和耐药性，其抗肿瘤效果相当有限。FEN1 是 DNA 修复系统的主要组成部分，在通过 DNA 复制和修复维持基因组稳定性方面发挥着重要作用。在这里，我们发现 FEN1 抑制剂能显著增强癌细胞对低剂量喜树碱的敏感性。FEN1 抑制剂和 1 nM 喜树碱联合治疗可产生协同致死作用，在体外和体内均协同抑制癌细胞增殖，并显著介导细胞凋亡。我们的研究表明，靶向 FEN1 可能是一种针对肿瘤的癌症治疗的有效策略。
