The key cellular senescence related molecule RRM2 regulates prostate cancer progression and resistance to docetaxel treatment
Abstract Background Prostate cancer is a leading cause of cancer-related deaths among men worldwide. Docetaxel chemotherapy has proven effective in improving overall survival in patients with castration-resistant prostate cancer (CRPC), but drug resistance remains a considerable clinical challenge....
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Cell & Bioscience |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13578-023-01157-6 |
| _version_ | 1797273084264185856 |
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| author | Bisheng Cheng Lingfeng Li Yongxin Wu Tianlong Luo Chen Tang Qiong Wang Qianghua Zhou Jilin Wu Yiming Lai Dingjun Zhu Tao Du Hai Huang |
| author_facet | Bisheng Cheng Lingfeng Li Yongxin Wu Tianlong Luo Chen Tang Qiong Wang Qianghua Zhou Jilin Wu Yiming Lai Dingjun Zhu Tao Du Hai Huang |
| author_sort | Bisheng Cheng |
| collection | DOAJ |
| description | Abstract Background Prostate cancer is a leading cause of cancer-related deaths among men worldwide. Docetaxel chemotherapy has proven effective in improving overall survival in patients with castration-resistant prostate cancer (CRPC), but drug resistance remains a considerable clinical challenge. Methods We explored the role of Ribonucleotide reductase subunit M2 (RRM2), a gene associated with senescence, in the sensitivity of prostate cancer to docetaxel. We evaluated the RRM2 expression, docetaxel resistance, and ANXA1 expression in prostate cancer cell lines and tumour xenografts models. In addition, We assessed the impact of RRM2 knockdown, ANXA1 over-expression, and PI3K/AKT pathway inhibition on the sensitivity of prostate cancer cells to docetaxel. Furthermore, we assessed the sensitivity of prostate cancer cells to the combination treatment of COH29 and docetaxel. Results Our results demonstrated a positive association between RRM2 expression and docetaxel resistance in prostate cancer cell lines and tumor xenograft models. Knockdown of RRM2 increased the sensitivity of prostate cancer cells to docetaxel, suggesting its role in mediating resistance. Furthermore, we observed that RRM2 stabilizes the expression of ANXA1, which in turn activates the PI3K/AKT pathway and contributes to docetaxel resistance. Importantly, we found that the combination treatment of COH29 and docetaxel resulted in a synergistic effect, further augmenting the sensitivity of prostate cancer cells to docetaxel. Conclusion Our findings suggest that RRM2 regulates docetaxel resistance in prostate cancer by stabilizing ANXA1-mediated activation of the PI3K/AKT pathway. Targeting RRM2 or ANXA1 may offer a promising therapeutic strategy to overcome docetaxel resistance in prostate cancer. Graphical Abstract |
| first_indexed | 2024-03-07T14:38:31Z |
| format | Article |
| id | doaj.art-1aa8e12d565f4544be983a134d375065 |
| institution | Directory Open Access Journal |
| issn | 2045-3701 |
| language | English |
| last_indexed | 2024-03-07T14:38:31Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj.art-1aa8e12d565f4544be983a134d3750652024-03-05T20:29:04ZengBMCCell & Bioscience2045-37012023-11-0113112010.1186/s13578-023-01157-6The key cellular senescence related molecule RRM2 regulates prostate cancer progression and resistance to docetaxel treatmentBisheng Cheng0Lingfeng Li1Yongxin Wu2Tianlong Luo3Chen Tang4Qiong Wang5Qianghua Zhou6Jilin Wu7Yiming Lai8Dingjun Zhu9Tao Du10Hai Huang11Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Urology, Nanfang Hospital, Southern Medical UniversityDepartment of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Obstetrics and Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityDepartment of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen UniversityAbstract Background Prostate cancer is a leading cause of cancer-related deaths among men worldwide. Docetaxel chemotherapy has proven effective in improving overall survival in patients with castration-resistant prostate cancer (CRPC), but drug resistance remains a considerable clinical challenge. Methods We explored the role of Ribonucleotide reductase subunit M2 (RRM2), a gene associated with senescence, in the sensitivity of prostate cancer to docetaxel. We evaluated the RRM2 expression, docetaxel resistance, and ANXA1 expression in prostate cancer cell lines and tumour xenografts models. In addition, We assessed the impact of RRM2 knockdown, ANXA1 over-expression, and PI3K/AKT pathway inhibition on the sensitivity of prostate cancer cells to docetaxel. Furthermore, we assessed the sensitivity of prostate cancer cells to the combination treatment of COH29 and docetaxel. Results Our results demonstrated a positive association between RRM2 expression and docetaxel resistance in prostate cancer cell lines and tumor xenograft models. Knockdown of RRM2 increased the sensitivity of prostate cancer cells to docetaxel, suggesting its role in mediating resistance. Furthermore, we observed that RRM2 stabilizes the expression of ANXA1, which in turn activates the PI3K/AKT pathway and contributes to docetaxel resistance. Importantly, we found that the combination treatment of COH29 and docetaxel resulted in a synergistic effect, further augmenting the sensitivity of prostate cancer cells to docetaxel. Conclusion Our findings suggest that RRM2 regulates docetaxel resistance in prostate cancer by stabilizing ANXA1-mediated activation of the PI3K/AKT pathway. Targeting RRM2 or ANXA1 may offer a promising therapeutic strategy to overcome docetaxel resistance in prostate cancer. Graphical Abstracthttps://doi.org/10.1186/s13578-023-01157-6RRM2Prostate cancerChemotherapyDocetaxelOncology |
| spellingShingle | Bisheng Cheng Lingfeng Li Yongxin Wu Tianlong Luo Chen Tang Qiong Wang Qianghua Zhou Jilin Wu Yiming Lai Dingjun Zhu Tao Du Hai Huang The key cellular senescence related molecule RRM2 regulates prostate cancer progression and resistance to docetaxel treatment Cell & Bioscience RRM2 Prostate cancer Chemotherapy Docetaxel Oncology |
| title | The key cellular senescence related molecule RRM2 regulates prostate cancer progression and resistance to docetaxel treatment |
| title_full | The key cellular senescence related molecule RRM2 regulates prostate cancer progression and resistance to docetaxel treatment |
| title_fullStr | The key cellular senescence related molecule RRM2 regulates prostate cancer progression and resistance to docetaxel treatment |
| title_full_unstemmed | The key cellular senescence related molecule RRM2 regulates prostate cancer progression and resistance to docetaxel treatment |
| title_short | The key cellular senescence related molecule RRM2 regulates prostate cancer progression and resistance to docetaxel treatment |
| title_sort | key cellular senescence related molecule rrm2 regulates prostate cancer progression and resistance to docetaxel treatment |
| topic | RRM2 Prostate cancer Chemotherapy Docetaxel Oncology |
| url | https://doi.org/10.1186/s13578-023-01157-6 |
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