ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Celastrol increases anoikis sensitivity to suppress triple-negative breast cancer via EGFR pathway and p-EMT state regulation
Xiangpeng Wang 1
Jue Yang 1
Xiuyun Bai 1
Rongjun Deng 1
Wanting Ye 1
Qiqiong Liu 1
Ying Xing 1
Yuxing Yao 1
Aiping Lyu 2
Cheng Lu 3
Yuanyan Liu 1
1. Beijing University of Chinese Medicine, Beijing, China
2. Hong Kong Baptist University, Hong Kong, Hong Kong, SAR China
3. China Academy of Chinese Medical Sciences, Beijing, China
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Abstract
Faced with the highly malignant threat of metastatic triple-negative breast cancer (TNBC), the effect of traditional chemical agents is limited, and new anti-metastasis drug remains to be explored. Celastrol (Cel) is a bioactive compound derived from Tripterygium wilfordii with significant anti-neoplastic effects in various cancers. In this study, we investigated the potential anti-metastatic effects of Cel on anoikis resistant TNBC cells (TNBC-AR) cells, including MDA-MB-231-AR cells and BT-549-AR cells. Using CCK-8 and colony formation assay, we demonstrated that Cel could inhibit the proliferation of MDA-MB-231-AR cells and BT-549-AR cells with IC50 value of 1.510 μM and 1.673 μM, respectively. The results of wound healing and transwell assays showed that Cel could potently inhibit the invasion and migration of TNBC-AR cells. Aggregation and flow cytometry experiments showed that Cel could inhibit the clusters formation and enhance the anoikis of TNBC-AR cells on the suspension conditions. Then we conducted bioinformatics analysis, western blotting, and intervention experiments to explore the molecular mechanisms of Cel's anti-metastasis effects. The results of these experiments discovered that Cel treatment suppressed the p-EMT state in TNBC-AR cells, and this effect correlated with a reduction in EGFR/MEK/ERK pathway activation. Our findings suggest that Cel may be a promising candidate for therapeutic treatments of metastatic TNBC.
Summary
Keywords
Anoikis, Celastrol, circulating tumor cells, Triple-negative breast cancer, Tumor metastasis
Received
17 November 2025
Accepted
18 February 2026
Copyright
© 2026 Wang, Yang, Bai, Deng, Ye, Liu, Xing, Yao, Lyu, Lu and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Aiping Lyu; Cheng Lu; Yuanyan Liu
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