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 |
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United States
John Wiley & Sons, Inc
01.12.2019
John Wiley and Sons Inc Wiley |
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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.
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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AbstractList | BackgroundCervical 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.MethodsWestern 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.ResultsOur 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.ConclusionFEN1 inhibitor SC13 could sensitize radiotherapy of cervical cancer cell. 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. 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. 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. 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. 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. FEN1 inhibitor SC13 could sensitize radiotherapy of cervical cancer cell. 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. 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. |
Author | Liu, Song‐Bai Xu, Xiang‐Bin Deng, Sheng‐Ming Guo, Wei‐Qiang Hu, He‐Juan Li, Dong‐Yin Wang, Jian‐Ping Chang, Hong Guo, Zhigang Du, Jia‐Hui Wang, Xiao‐Xiao Li, Jin‐Li Song, Yao‐Hua Sun, Min‐Xuan Wu, Yi‐Wei |
AuthorAffiliation | 6 Cyrus Tang Hematology Center Collaborative Innovation Center of Hematology Soochow University Suzhou China 7 Jiangsu Key Laboratory for Molecular and Medical Biotechnology College of Life Science Nanjing Normal University Nanjing China 3 Department of Nuclear Medicine The Affiliated Hospital of Soochow University Suzhou China 1 Department of Radiation Oncology The Affiliated Hospital of Soochow University Suzhou China 8 Jiangsu Key Laboratory of Medical Optics Suzhou Institute of Biomedical Engineering and Technology Chinese Academy of Sciences Suzhou China 2 Suzhou Key Laboratory for Medical Biotechnology Suzhou Vocational Health College Suzhou China 4 College of Food Science and Technology Hainan University Haikou China 5 School of Chemistry, Biology and Materials Engineering Suzhou University of Science and Technology Suzhou China |
AuthorAffiliation_xml | – name: 7 Jiangsu Key Laboratory for Molecular and Medical Biotechnology College of Life Science Nanjing Normal University Nanjing China – name: 8 Jiangsu Key Laboratory of Medical Optics Suzhou Institute of Biomedical Engineering and Technology Chinese Academy of Sciences Suzhou China – name: 2 Suzhou Key Laboratory for Medical Biotechnology Suzhou Vocational Health College Suzhou China – name: 4 College of Food Science and Technology Hainan University Haikou China – name: 6 Cyrus Tang Hematology Center Collaborative Innovation Center of Hematology Soochow University Suzhou China – name: 1 Department of Radiation Oncology The Affiliated Hospital of Soochow University Suzhou China – name: 3 Department of Nuclear Medicine The Affiliated Hospital of Soochow University Suzhou China – name: 5 School of Chemistry, Biology and Materials Engineering Suzhou University of Science and Technology Suzhou China |
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Copyright | 2019 The Authors. published by John Wiley & Sons Ltd. 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. |
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Keywords | radiotherapy targeted therapy FEN1 cervical cancer |
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License | Attribution 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
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Notes | Jin‐Li Li, Jian‐Ping Wang, Hong Chang and Sheng‐Ming Deng contributed equally to this work and as the first author. |
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Cervical cancer is one of the most common causes of cancer‐associated mortality among affected women in the world. At present, treatment with weekly... 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... Abstract Background Cervical cancer is one of the most common causes of cancer‐associated mortality among affected women in the world. At present, treatment... BackgroundCervical cancer is one of the most common causes of cancer‐associated mortality among affected women in the world. At present, treatment with weekly... 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... Abstract Background Cervical cancer is one of the most common causes of cancer‐associated mortality among affected women in the world. At present, treatment... |
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SubjectTerms | 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 |
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Title | FEN1 inhibitor increases sensitivity of radiotherapy in cervical cancer cells |
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