文献类型：期刊文献

英文题名：Celastrol attenuates the invasion and migration and augments the anticancer effects of olaparib in prostate cancer

作者：Huang, Mengqiu Chen, Lin Ma, Xiaoyan Xu, Houqiang

第一作者：Huang, Mengqiu

通信作者：Xu, HQ[1];Xu, HQ[2];Xu, HQ[3];Xu, HQ[4]

机构：[1]Guiyang Univ, Coll Biol & Environm Engn, Guiyang 550005, Guizhou, Peoples R China;[2]Guizhou Univ, Minist Educ, Key Lab Anim Genet Breeding & Reprod Plateau Mount, Guiyang, Guizhou, Peoples R China;[3]Guizhou Univ, Coll Anim Sci, Guiyang, Guizhou, Peoples R China;[4]Zunyi Med Univ, Affiliated Hosp, Dept Ophthalmol, Zunyi, Guizhou, Peoples R China;[5]Guizhou Inst Technol, Coll Food & Pharmaceut Engn, Guiyang, Guizhou, Peoples R China;[6]Guizhou Univ, Sch Med, Dept Biomed, 2708 Huaxi Rd South, Guiyang 550025, Guizhou, Peoples R China

第一机构：Guiyang Univ, Coll Biol & Environm Engn, Guiyang 550005, Guizhou, Peoples R China

通信机构：corresponding author), Guiyang Univ, Coll Biol & Environm Engn, Guiyang 550005, Guizhou, Peoples R China;corresponding author), Guizhou Univ, Minist Educ, Key Lab Anim Genet Breeding & Reprod Plateau Mount, Guiyang, Guizhou, Peoples R China;corresponding author), Guizhou Univ, Coll Anim Sci, Guiyang, Guizhou, Peoples R China;corresponding author), Guizhou Univ, Sch Med, Dept Biomed, 2708 Huaxi Rd South, Guiyang 550025, Guizhou, Peoples R China.

年份：2024

卷号：24

期号：1

外文期刊名：CANCER CELL INTERNATIONAL

收录：;Scopus(收录号：2-s2.0-85208132647);WOS:【SCI-EXPANDED(收录号:WOS:001342231900003)】；

基金：No applicable.

语种：英文

外文关键词：Prostate Cancer; HSP90AB1; PARP1; Olaparib; Celastrol; PI3K/AKT pathway

摘要：BackgroundProstate 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.MethodsThis 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.ResultsOur 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.ConclusionsThe 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.