FEN1 inhibitor synergizes with low-dose camptothecin to induce increased cell killing via the mitochondria mediated apoptotic pathway
Camptothecin has been used in tumor therapy for a long time but its antitumor effect is rather limited due to the side effect and the drug resistance. FEN1, a major component of DNA repair systems, plays important roles in maintaining genomic stability via DNA replication and repair. Here we found t...
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| Veröffentlicht in: | Gene therapy 2022-08, Vol.29 (7-8), p.407-417 |
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| container_issue | 7-8 |
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| container_title | Gene therapy |
| container_volume | 29 |
| creator | Wu, Ting Zhu, Hongqiao Zhang, Miaomiao Sun, Yuling Yang, Yongjing Gu, Lili Zhang, Jing Mu, Dan Wu, Congye Hu, Zhigang Jiang, Longwei Jia, Shaochang Zhang, Ying He, Lingfeng Pan, Fei-Yan Guo, Zhigang |
| description | Camptothecin has been used in tumor therapy for a long time but its antitumor effect is rather limited due to the side effect and the drug resistance. FEN1, a major component of DNA repair systems, plays important roles in maintaining genomic stability
via
DNA replication and repair. Here we found that FEN1 inhibitor greatly sensitizes cancer cells to low-dose camptothecin. The combinative treatment of FEN1 inhibitor and 1 nM camptothecin induced a synthetic lethal effect, which synergistically suppressed cancer cell proliferation and significantly mediated apoptosis both in vitro and in vivo. Our study suggested that targeting FEN1 could be a potent strategy for tumor-targeting cancer therapy. |
| doi_str_mv | 10.1038/s41434-020-00215-9 |
| format | Article |
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via
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Our study suggested that targeting FEN1 could be a potent strategy for tumor-targeting cancer therapy.</description><subject>13</subject><subject>13/2</subject><subject>14</subject><subject>38</subject><subject>631/337/1427</subject><subject>631/61/201/2110</subject><subject>64</subject><subject>64/60</subject><subject>82</subject><subject>96/2</subject><subject>Antibodies</subject><subject>Antitumor activity</subject><subject>Apoptosis</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Camptothecin</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Cell Biology</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Cell proliferation</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA biosynthesis</subject><subject>DNA damage</subject><subject>DNA repair</subject><subject>Drug dosages</subject><subject>Drug resistance</subject><subject>FEN1 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via
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| subjects | 13 13/2 14 38 631/337/1427 631/61/201/2110 64 64/60 82 96/2 Antibodies Antitumor activity Apoptosis Biomedical and Life Sciences Biomedicine Camptothecin Cancer Cancer therapies Cell Biology Cell cycle Cell growth Cell proliferation Deoxyribonucleic acid DNA DNA biosynthesis DNA damage DNA repair Drug dosages Drug resistance FEN1 protein Gene Expression Gene Therapy Human Genetics Metastasis Mitochondria Mitochondrial DNA Nanotechnology Prostate Tumors |
| title | FEN1 inhibitor synergizes with low-dose camptothecin to induce increased cell killing via the mitochondria mediated apoptotic pathway |
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