Research Articles:
Cell Stress, Vol. 10, No. 1, pp. 53 - 63; doi: 10.15698/cst2026.07.319
Triptolide inhibits ovarian cancer growth and metastasis via reprogramming of tumor-associated macrophages
1 Institute of Oncology, Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China. 2 Science and Technology Innovation Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China. 3 Central Laboratory for Science and Technology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. 4 Department of Gynecology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China. 5 Department of Traditional Chinese Gynecology, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, China.
Keywords: Triptolide, ovarian cancer, macrophage reprograming, Nrf2, tumor-associated macrophages (TAMs)
Received originally: 20/07/2025 Received in revised form: 28/04/2026
Accepted: 07/05/2026
Published: 07/07/2026
Correspondence:
Hong Yang, Institute of Oncology, Department of Gynecology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 274 Zhijiang Middle Road, Jing’an District, Shanghai 200071, China; 13585517187@aliyun.com
Chaoqin Yu, Department of Traditional Chinese Gynecology, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China; chqyu81@163.com
Ziqi Chen, Institute of Oncology, Science and Technology Innovation Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 274 Zhijiang Middle Road, Jing’an District, Shanghai 200071, China; Tel: +862156639828; ziqichentcm@shutcm.edu.cn
Conflict of interest statement: The author has declared that no competing interests exist.
Please cite this article as: Ziqi Chen, Jie Zhang, Jianting Lao, Chaoqin Yu, Hong Yang (2026). Triptolide inhibits ovarian cancer growth and metastasis via reprogramming of tumor-associated macrophages. Cell Stress 10: 53-63. doi: 10.15698/cst2026.07.319
Abstract
Triptolide, an extract from the Chinese herb Thunder God Vine, a compound renowned for its anti-cancer properties, exhibits an elusive mechanism of action. While extensive research has elucidated its direct effects on cancer cells, the indirect impact on non-tumor cells within the cancer microenvironment remains poorly understood. In this study, we investigated the influence of Triptolide on tumor-associated macrophages (TAMs), pivotal contributors to ovarian cancer progression. Using cell culture and promoter assay, cellular viability assessment, cell clock assay, transwell assays, flow cytometry, ELISA, TUNEL staining, and mouse models, we found that Triptolide does not significantly affect macrophage proliferation or survival; instead, it induces differentiation of naive macrophages towards the M1 phenotype and reprograms M2- polarized macrophages into a similar inflammatory state. These observations suggest that modulation of TAMs may partially underlie Triptolide’s hindrance of ovarian cancer progression. Mechanistically, we reveal that Triptolide inhibits Nrf2 transcription – a master regulator governing antiinflammatory responses in macrophages. Functional gain- and loss-offunction studies further confirmed that Nrf2 inhibition is essential for Triptolide-mediated TAM reprogramming and subsequent suppression of cancer cell progression. Co-culturing with macrophages substantially enhances ovarian cancer cell growth, invasion, and migration; however, all these effects are abrogated by treatment with Triptolide. Collectively, our findings indicate that the suppression of ovarian cancer by Triptolide is mediated in part through its capacity to reprogram TAMs via the Nrf2 pathway.
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AUTHOR CONTRIBUTIONS
Ziqi Chen: Conceptualization, Investigation, Formal analysis, Validation, Writing - original draft, Writing - review & editing, Funding acquisition. Jie Zhang: Investigation, Writing-original draft, Funding acquisition. Jianting Lao: Investigation, Data curation. Hong Yang: Conceptualization, Project administration, Supervision, Funding acquisition. Chaoqin Yu:Project administration, Supervision. All authors read and approved the final manuscript.
ACKNOWLEDGMENTS
The work was supported by National Natural Science Foundation of China (82304777, 82174428), Shanghai Oriental Talent Program (Youth Project, QNWS2025010), Shanghai Sailing Program (23YF1442800), the Young talents project of Shanghai Municipal Health Commission (2022YQ066). Traditional Chinese Medicine Science and Technology Development Project of Shanghai Medical Innovation & Development Foundation (WL-HBQN-2021004K, WL-QNPY-2022004K).
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© 2026
Triptolide inhibits ovarian cancer growth and metastasis via reprogramming of tumor-associated macrophages by Chen et al. is licensed under a Creative Commons Attribution 4.0 International License.
