Open Access

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
  • View Affiliations

  • 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.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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.
View Figures
View References

Related Articles

Journal Cover

May-2021
Volume 45 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Zhong Y, Le F, Cheng J, Luo C, Zhang X, Wu X, Xu F, Zuo Q and Tan B: Triptolide inhibits JAK2/STAT3 signaling and induces lethal autophagy through ROS generation in cisplatin‑resistant SKOV3/DDP ovarian cancer cells. Oncol Rep 45: 69, 2021.
APA
Zhong, Y., Le, F., Cheng, J., Luo, C., Zhang, X., Wu, X. ... Tan, B. (2021). Triptolide inhibits JAK2/STAT3 signaling and induces lethal autophagy through ROS generation in cisplatin‑resistant SKOV3/DDP ovarian cancer cells. Oncology Reports, 45, 69. https://doi.org/10.3892/or.2021.8020
MLA
Zhong, Y., Le, F., Cheng, J., Luo, C., Zhang, X., Wu, X., Xu, F., Zuo, Q., Tan, B."Triptolide inhibits JAK2/STAT3 signaling and induces lethal autophagy through ROS generation in cisplatin‑resistant SKOV3/DDP ovarian cancer cells". Oncology Reports 45.5 (2021): 69.
Chicago
Zhong, Y., Le, F., Cheng, J., Luo, C., Zhang, X., Wu, X., Xu, F., Zuo, Q., Tan, B."Triptolide inhibits JAK2/STAT3 signaling and induces lethal autophagy through ROS generation in cisplatin‑resistant SKOV3/DDP ovarian cancer cells". Oncology Reports 45, no. 5 (2021): 69. https://doi.org/10.3892/or.2021.8020