Changzhou No. 7 People's Hospital, China; Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing, 210023, China.
Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing, 210023, China.
DNA Repair (Amst). 2018 Mar;63:1-9. doi: 10.1016/j.dnarep.2018.01.003. Epub 2018 Jan 9.
Studies on cervical cancer are urgently required to improve clinical outcomes. As a major anticancer drug for cervical cancer, paclitaxel has been used for many years in clinical therapy but its therapeutic efficacy is limited by common obstacle from cancer cells. The enhanced DNA repair pathways of cancer cells have been proved to survive DNA damage induced by chemotherapeutic drug. Inhibitors of specific DNA repair pathway can sensitize cancer cells to the treatment of chemotherapeutic drugs. In this paper we found that the effect of paclitaxel can be significantly improved when used in combination with FEN1 inhibitor SC13, suggesting a synergistic mechanism between the two compounds. Our studies suggest that FEN1 inhibition could be a novel strategy of tumor-targeting therapy for cervical cancer. Our work also revealed that paclitaxel demonstrates stronger synergistic effect with SC13 than other common used chemical drugs such as doxorubicin, carboplatin or camptothecin on cervical cancer cells.
为了提高临床疗效，迫切需要对宫颈癌进行研究。紫杉醇作为宫颈癌的主要抗癌药物，多年来已在临床治疗中应用，但由于癌细胞普遍存在障碍，其治疗效果有限。已经证实癌细胞增强的 DNA 修复途径能够使癌细胞存活于化疗药物诱导的 DNA 损伤。特定的 DNA 修复途径抑制剂可使癌细胞对化疗药物的治疗更敏感。在本文中，我们发现紫杉醇与 FEN1 抑制剂 SC13 联合使用时，其效果可显著提高，表明这两种化合物之间存在协同作用机制。我们的研究表明，FEN1 抑制可能是宫颈癌的一种新型肿瘤靶向治疗策略。我们的工作还表明，紫杉醇与 SC13 联合使用对宫颈癌细胞的协同作用强于其他常用的化学药物，如多柔比星、卡铂或喜树碱。
