FEN1 inhibitor increases sensitivity of radiotherapy in cervical cancer cells
Authors:
Open Access
- 31 October 2019
- journal article
- research article
- Published by Wiley in Cancer Medicine
- Vol. 8 (18) , 7774-7780
Abstract
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.Keywords
Funding Information
- National Natural Science Foundation of China (31701198, 81601522)
- Natural Science Foundation of Jiangsu Province (BK20170386, BK20160348)
This publication has 32 references indexed in Scilit:
- Flap Endonuclease 1Annual Review of Biochemistry, 2013
- Functional regulation of FEN1 nuclease and its link to cancerNucleic Acids Research, 2010
- Cellular Responses to Cisplatin‐Induced DNA DamageJournal of Nucleic Acids, 2010
- DNA Damage, Mutagenesis, and DNA RepairJournal of Nucleic Acids, 2010
- Multiple but dissectible functions of FEN‐1 nucleases in nucleic acid processing, genome stability and diseasesBioEssays, 2005
- Radiotherapy and cellular signallingThe Lancet Oncology, 2001
- Cisplatin, Radiation, and Adjuvant Hysterectomy Compared with Radiation and Adjuvant Hysterectomy for Bulky Stage IB Cervical CarcinomaNew England Journal of Medicine, 1999
- Concurrent Cisplatin-Based Radiotherapy and Chemotherapy for Locally Advanced Cervical CancerNew England Journal of Medicine, 1999
- The FEN‐1 family of structure‐specific nucleases in eukaryotic dna replication, recombination and repairBioEssays, 1997
- X-Ray Structure of the Major Adduct of the Anticancer Drug Cisplatin with DNA: cis -[Pt(NH 3 ) 2 {d(pGpG)}]Science, 1985