Work

Celastrol attenuates the invasion and migration and augments the anticancer effects of olaparib in prostate cancer

Year: 2024

Type: article

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.

Source: Cancer Cell International

DOI: 10.1186/s12935-024-03542-8

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

Institutions: Guiyang University, Zunyi Medical University, Affiliated Hospital of Zunyi Medical College, Guizhou Institute of Technology, Guizhou University

Language: English

Topic: Prostate Cancer Treatment and Research

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,990