Triptolide inhibits ovarian cancer growth and metastasis via reprogramming of tumor-associated macrophages
Authors:Ziqi Chen1,2,a, Jie Zhang3,a, Jianting Lao4, Chaoqin Yu5 and Hong Yang1,4
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)
Corresponding Author(s):
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
© 2026 Chen et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
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.