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

Zhang,Haiyan; Li,Jianhua; Li,Guang; Wang,Surong

doi:10.3892/mmr.2016.5894

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

Authors:
- Haiyan Zhang
- Jianhua Li
- Guang Li
- Surong Wang
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Affiliations: Gynaecology Ward‑1, Department of Gynaecology, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China, Department of Gynaecology Lab, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China, Department of Gastrointestinal Surgery, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China, Gynaecology Ward‑3, Department of Gynaecology, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China
Published online on: October 26, 2016 https://doi.org/10.3892/mmr.2016.5894
Pages: 5363-5368

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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.

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