Mechanisms of celastrol for ovarian cancer: based on quantitative proteomics

doi:10.19803/j.1672-8629.20230197

Abstract

Abstract: Objective To explore the inhibitory effect of celastrol on proliferation and migration of ovarian cancer cells and the molecular mechanism. Methods The ability of celastrol to inhibit the proliferation and migration of ovarian cancer cells was confirmed by MTT and wound healing assays. Proteomics was performed to discriminate the differentially expressed proteins (DEPs) associated with the inhibitory effects of celastrol on ovarian cells. EMT markers (cadherin switch) and key proteins that regulated cell migration (CD44 and HMGB) in ovarian cancer cells were detected using Western blot. The effect of celastrol on reactive oxygen species (ROS) production in ovarian cancer cells was determined via immunofluorescence measurement. Results Celastrol significantly inhibited the proliferation and migration of SKOV3 and OVCAR3 cells. 396 DEPs were identified in ovarian cells treated with celastrol (126 up-regulated and 270 down-regulated) based on proteomics. The analysis of both GO and KEGG pathways showed that the multi-target anti-tumor activity of celastrol was related to cell migration, inflammation and hypoxia. Celastrol inhibited EMT by down-regulating N-cadherin and up-regulating E-cadherin. Celastrol also retarded the healing of ovarian cancer cells by inhibiting the expressions CD44, HMGB1 and HMGB2. Conclusion Proteomics studies have found that celastrol has multi-targeted anti-ovarian cancer activities. Celastrol can inhibit the migration and proliferation of ovarian cancer cells by inhibiting the process of EMT and inducing the production of ROS.

Key words: ovarian cancer, celastrol, quantitative proteomics, epithelial mesenchymal transformation, migration

CLC Number:

MA Qihong, SHI Yuanyuan, CHEN Fangfang, WU Kang, BU Zixuan, LU Tiangong. Mechanisms of celastrol for ovarian cancer: based on quantitative proteomics[J]. Chinese Journal of Pharmacovigilance, 2023, 20(7): 721-727.

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