FEN1 inhibitor increases sensitivity of radiotherapy in cervical cancer cells

• Published in: Cancer medicine (Malden, MA) Vol. 8; no. 18; pp. 7774 - 7780
• Main Authors: Li, Jin‐Li, Wang, Jian‐Ping, Chang, Hong, Deng, Sheng‐Ming, Du, Jia‐Hui, Wang, Xiao‐Xiao, Hu, He‐Juan, Li, Dong‐Yin, Xu, Xiang‐Bin, Guo, Wei‐Qiang, Song, Yao‐Hua, Guo, Zhigang, Sun, Min‐Xuan, Wu, Yi‐Wei, Liu, Song‐Bai
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.12.2019; John Wiley and Sons Inc; Wiley
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Apoptosis - radiation effects; Cancer Biology; Cancer therapies; Cell Line, Tumor; Cell Survival - drug effects; Cell Survival - radiation effects; Cervical cancer; Cervix; Cisplatin; CRISPR; Deoxyribonucleic acid; Disease Models, Animal; DNA; DNA damage; DNA repair; Enzyme Inhibitors - pharmacology; Female; FEN1; FEN1 protein; Flap Endonucleases - antagonists & inhibitors; Flap Endonucleases - genetics; Flap Endonucleases - metabolism; Gene Expression; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Neoplastic - radiation effects; Grants; Growth inhibition; HeLa Cells; Humans; Immunoglobulins; Ionizing radiation; Lung cancer; Mice; Original Research; Proteins; Radiation therapy; Radiation Tolerance - drug effects; Radiation, Ionizing; Radiation-Sensitizing Agents - pharmacology; radiotherapy; Science; targeted therapy; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - pathology; Xenograft Model Antitumor Assays; Xenografts; China; radiotherapy; targeted therapy; FEN1; cervical cancer
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.2615

Background Cervical cancer is one of the most common causes of cancer‐associated mortality among affected women in the world. At present, treatment with weekly cisplatin plus ionizing radiation (IR) therapy is the standard regimen for cervical cancer, especially for locally advanced cervical cancer. The purpose of this study is to determine whether FEN1 inhibitors could enhance the therapeutic effect of IR therapy. Methods Western blot was applied to determine the expression of FEN1‐ and apoptosis‐related proteins. Cell growth inhibition assay and colony formation assay were used to determine the effects of FEN1 inhibitor and IR exposure for Hela cells in vitro. CRISPR technology was used to knockdown FEN1 expression level of 293T cells, and tumor xenograft in nude mice was employed to determine the effects of FEN1 inhibitor and IR exposure on tumor growth in vivo. Results Our data revealed that FEN1 is overexpressed in HeLa cell and can be upregulated further by IR. We also demonstrated that FEN1 inhibitor enhances IR sensitivity of cervical cancer in vitro and in vivo. Conclusion FEN1 inhibitor SC13 could sensitize radiotherapy of cervical cancer cell. FEN1 is overexpressed in HeLa cell and the expression can be upregulated further by IR. FEN1 inhibitor enhances IR sensitivity of cervical cancer, and this enhancement effect was largely due to the impairment of DNA damage repair mechanism resulting from FEN1 inhibition, leading to apoptosis of cancer cells.