Triptolide inhibits JAK2/STAT3 signaling and induces lethal autophagy through ROS generation in cisplatin‑resistant SKOV3/DDP ovarian cancer cells

Zhong,Yanying; Le,Fuyin; Cheng,Jiao; Luo,Chen; Zhang,Xiali; Wu,Xingwu; Xu,Fang; Zuo,Qi; Tan,Buzhen

doi:10.3892/or.2021.8020

Triptolide inhibits JAK2/STAT3 signaling and induces lethal autophagy through ROS generation in cisplatin‑resistant SKOV3/DDP ovarian cancer cells

Authors:
- Yanying Zhong
- Fuyin Le
- Jiao Cheng
- Chen Luo
- Xiali Zhang
- Xingwu Wu
- Fang Xu
- Qi Zuo
- Buzhen Tan
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Affiliations: Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Tumour Immunology, School of Basic Medicine Sciences, Nanchang University Medical College, Nanchang, Jiangxi 330006, P.R. China, Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Laboratory Animal Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, P.R. China, Department of Obstetrics and Gynecology, The Third Hospital of Nanchang University, Nanchang, Jiangxi 330009, P.R. China
Published online on: March 19, 2021 https://doi.org/10.3892/or.2021.8020
Article Number: 69
Copyright: © Zhong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Advanced and recurrent ovarian cancer has a poor prognosis and is frequently resistant to numerous therapeutics; thus, safe and effective drugs are needed to combat this disease. Previous studies have demonstrated that triptolide (TPL) exhibits anticancer and sensitization effects against cisplatin (DDP)‑resistant ovarian cancer both in vitro and in vivo by inducing apoptosis; however, the involvement of autophagy induced by TPL in resistant ovarian carcinoma remains unclear. In the present study, the results revealed that TPL induced autophagy to facilitate SKOV3/DDP ovarian cancer cell death. The xenograft experiment revealed that the autophagy inhibitor CQ significantly reduced TPL‑mediated chemosensitization and tumor growth inhibition. Mechanically, TPL‑induced autophagy in SKOV3/DDP cells was associated with the induction of ROS generation and inhibition of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription‑3 (STAT3) pathway. The inhibitory effect of TPL on the JAK2/STAT3 pathway could be restored in the presence of the antioxidant NAC. Furthermore, it was further determined that TPL disrupted the interaction between Mcl‑1 and Beclin1, which was prevented by the JAK2/STAT3 signaling activator IL‑6. Overall, the present results revealed a novel molecular mechanism whereby TPL induced lethal autophagy through the ROS‑JAK2/STAT3 signaling cascade in SKOV3/DDP cells. The present study has provided the groundwork for future application of TPL in the treatment of ovarian cancer.

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