Celastrol attenuates the invasion and migration and augments the anticancer effects of olaparib in prostate cancer
Abstract Background Prostate cancer (PCa) is a leading malignancy among men globally, with rising incidence rates emphasizing the critical need for better detection and therapeutic approaches. The roles of HSP90AB1 and PARP1 in prostate cancer cells suggest potential targets for enhancing treatment...
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| Format: | Article |
| Language: | English |
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BMC
2024-10-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-024-03542-8 |
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| author | Mengqiu Huang Lin Chen Xiaoyan Ma Houqiang Xu |
| author_facet | Mengqiu Huang Lin Chen Xiaoyan Ma Houqiang Xu |
| author_sort | Mengqiu Huang |
| collection | DOAJ |
| description | Abstract Background Prostate cancer (PCa) is a leading malignancy among men globally, with rising incidence rates emphasizing the critical need for better detection and therapeutic approaches. The roles of HSP90AB1 and PARP1 in prostate cancer cells suggest potential targets for enhancing treatment efficacy. Methods This study investigated the overexpression of HSP90AB1 and PARP1 in prostate cancer cells and the impact of HSP90AB1 knockdown on the sensitivity of these cells to the PARP inhibitor olaparib. We also explored the combined effect of olaparib and celastrol, an HSP90 inhibitor, on the clonogenic survival, migration, proliferation, and overall viability of prostate cancer cells, alongside the modulation of the PI3K/AKT pathway. An in vivo PC3 xenograft mouse model was used to assess the antitumor effects of the combined treatment. Results Our findings revealed significant overexpression of HSP90AB1 and PARP1 in prostate cancer cells. Knockdown of HSP90AB1 increased cell sensitivity to olaparib. The combination of olaparib and celastrol significantly reduced prostate cancer cell survival, migration, proliferation, and enhanced cumulative DNA damage. Celastrol also downregulated the PI3K/AKT pathway, increasing cell susceptibility to olaparib. In vivo experiments demonstrated that celastrol and olaparib together exerted strong antitumor effects. Conclusions The study indicates that targeting both HSP90AB1 and PARP1 presents a promising therapeutic strategy for prostate cancer. The synergistic combination of celastrol and olaparib enhances the efficacy of treatment against prostate cancer, offering a potent approach to combat this disease. |
| format | Article |
| id | doaj-art-df19228ae1aa4ae3a4eac0a5fd55d607 |
| institution | OA Journals |
| issn | 1475-2867 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj-art-df19228ae1aa4ae3a4eac0a5fd55d6072025-08-20T02:12:03ZengBMCCancer Cell International1475-28672024-10-0124111210.1186/s12935-024-03542-8Celastrol attenuates the invasion and migration and augments the anticancer effects of olaparib in prostate cancerMengqiu Huang0Lin Chen1Xiaoyan Ma2Houqiang Xu3College of Biology and Environmental Engineering, Guiyang UniversityDepartment of Ophthalmology, Affiliated Hospital of Zunyi Medical UniversityCollege of Food and Pharmaceutical Engineering, Guizhou Institute of TechnologyCollege of Biology and Environmental Engineering, Guiyang UniversityAbstract Background Prostate cancer (PCa) is a leading malignancy among men globally, with rising incidence rates emphasizing the critical need for better detection and therapeutic approaches. The roles of HSP90AB1 and PARP1 in prostate cancer cells suggest potential targets for enhancing treatment efficacy. Methods This study investigated the overexpression of HSP90AB1 and PARP1 in prostate cancer cells and the impact of HSP90AB1 knockdown on the sensitivity of these cells to the PARP inhibitor olaparib. We also explored the combined effect of olaparib and celastrol, an HSP90 inhibitor, on the clonogenic survival, migration, proliferation, and overall viability of prostate cancer cells, alongside the modulation of the PI3K/AKT pathway. An in vivo PC3 xenograft mouse model was used to assess the antitumor effects of the combined treatment. Results Our findings revealed significant overexpression of HSP90AB1 and PARP1 in prostate cancer cells. Knockdown of HSP90AB1 increased cell sensitivity to olaparib. The combination of olaparib and celastrol significantly reduced prostate cancer cell survival, migration, proliferation, and enhanced cumulative DNA damage. Celastrol also downregulated the PI3K/AKT pathway, increasing cell susceptibility to olaparib. In vivo experiments demonstrated that celastrol and olaparib together exerted strong antitumor effects. Conclusions The study indicates that targeting both HSP90AB1 and PARP1 presents a promising therapeutic strategy for prostate cancer. The synergistic combination of celastrol and olaparib enhances the efficacy of treatment against prostate cancer, offering a potent approach to combat this disease.https://doi.org/10.1186/s12935-024-03542-8Prostate CancerHSP90AB1PARP1OlaparibCelastrolPI3K/AKT pathway |
| spellingShingle | Mengqiu Huang Lin Chen Xiaoyan Ma Houqiang Xu Celastrol attenuates the invasion and migration and augments the anticancer effects of olaparib in prostate cancer Cancer Cell International Prostate Cancer HSP90AB1 PARP1 Olaparib Celastrol PI3K/AKT pathway |
| title | Celastrol attenuates the invasion and migration and augments the anticancer effects of olaparib in prostate cancer |
| title_full | Celastrol attenuates the invasion and migration and augments the anticancer effects of olaparib in prostate cancer |
| title_fullStr | Celastrol attenuates the invasion and migration and augments the anticancer effects of olaparib in prostate cancer |
| title_full_unstemmed | Celastrol attenuates the invasion and migration and augments the anticancer effects of olaparib in prostate cancer |
| title_short | Celastrol attenuates the invasion and migration and augments the anticancer effects of olaparib in prostate cancer |
| title_sort | celastrol attenuates the invasion and migration and augments the anticancer effects of olaparib in prostate cancer |
| topic | Prostate Cancer HSP90AB1 PARP1 Olaparib Celastrol PI3K/AKT pathway |
| url | https://doi.org/10.1186/s12935-024-03542-8 |
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