FEN1 inhibitor increases sensitivity of radiotherapy in cervical cancer cells
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....
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Published in | Cancer medicine (Malden, MA) Vol. 8; no. 18; pp. 7774 - 7780 |
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Main Authors | , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
John Wiley & Sons, Inc
01.12.2019
John Wiley and Sons Inc Wiley |
Subjects | |
Online Access | Get full text |
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Summary: | 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. |
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Bibliography: | Jin‐Li Li, Jian‐Ping Wang, Hong Chang and Sheng‐Ming Deng contributed equally to this work and as the first author. |
ISSN: | 2045-7634 2045-7634 |
DOI: | 10.1002/cam4.2615 |