title: Effects of celastrol on enhancing apoptosis of ovarian cancer cells via the downregulation of microRNA‑21 and the suppression of the PI3K/Akt‑NF‑κB signaling pathway in an in vitro model of ovarian carcinoma.
abstract: Celastrol has previously been used to treat rheumatoid arthritis, bruises, back pain and additional diseases. At present, efficacy studies predominantly focus on the anti‑inflammatory, antioxidative and antitumor effects of celastrol. However, the effect of celastrol on ovarian cancer cells is not fully elucidated. In the present study, the effects of celastrol were investigated in ovarian cancer cells and the mechanisms involved were explored. In OVCAR3 cells, celastrol was observed to suppress cellular proliferation, induce apoptosis and increase caspase‑9 and ‑3 activity in a dose‑ and time‑dependent manner. The expression levels of microRNA‑21 (miRNA‑21) were reduced, in addition to a reduction in the levels of phosphoinositide 3‑kinase (PI3K)/p‑Akt‑NF (NF)‑κB following treatment with celastrol. Notably, reduced expression of miRNA‑21 replicated the effect of celastrol on OVCAR3 cells and inhibited the PI3K/p‑Akt‑NF‑κB signaling pathway in an in vitro model of ovarian carcinoma. To the best of our knowledge this is the first study to indicate that celastrol may represent a potential agent for the treatment of human ovarian carcinoma, via the induction of apoptosis through the downregulation of miRNA‑21 and the PI3K/Akt‑NF‑κB signaling pathway in an in vitro model of ovarian carcinoma.
authors.affiliation: Gynaecology Ward‑1, Department of Gynaecology, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Gynaecology Lab, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Surgery, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China.
authors.forename: Guang
authors.initials: G
authors.lastname: Li
authors.affiliation: Gynaecology Ward‑3, Department of Gynaecology, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China.
authors.forename: Surong
authors.initials: S
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism*; D053978:Pentacyclic Triterpenes; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D053148:Caspase 3; D053453:Caspase 9; D035683:MicroRNAs; D016328:NF-kappa B; D053978:Pentacyclic Triterpenes; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D014315:Triterpenes; C524940:MIRN21 microRNA, human; C050414:celastrol