Euphorbia factor L2 suppresses the generation of liver metastatic ascites in breast cancer via inhibiting NLRP3 inflammasome activation

Jiang,Dongjing; Liu,Xun; Tan,Rulan; Zhu,Ye; Zhang,Li

doi:10.3892/ijmm.2023.5332

Euphorbia factor L2 suppresses the generation of liver metastatic ascites in breast cancer via inhibiting NLRP3 inflammasome activation

This article is part of the special Issue: The Biology and Clinical Utility of Circulating Tumor Cells
Authors:
- Dongjing Jiang
- Xun Liu
- Rulan Tan
- Ye Zhu
- Li Zhang
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Affiliations: Traditional Chinese Medicine and Research Office, Suzhou Vocational Health College, Suzhou, Jiangsu 215000, P.R. China, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P.R. China
Published online on: December 4, 2023 https://doi.org/10.3892/ijmm.2023.5332
Article Number: 8
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Metastasis is the leading cause of death in patients with breast cancer, in part due to the lack of effective treatments. Euphorbia factor L2 (EFL2) is a diterpenoid extracted from Euphorbia lathyris L. seeds, which has attracted increasing attention in recent years due to its anticancer effect. However, the role and molecular mechanism of EFL2 in breast cancer liver metastasis remain unclear. In the present study, a breast cancer liver metastasis model was constructed and the effect of EFL2 on ascites generation in mice was examined. H&E staining detected inflammatory cells and tumor cells in the liver, small intestine and tumor tissues. Western blotting and reverse transcription‑quantitative PCR were used to detect the protein and mRNA expression of NLR family pyrin domain containing‑3 (NLRP3) and related molecules in tumor tissues. Immunohistochemistry was used to detect the levels of CD4 and CD8 T cells in tumor tissue and immunofluorescence was used to further detect the expression level of NLRP3. Finally, the aforementioned experiments were further verified by overexpressing NLPR3. It was found that EFL2 inhibited generation of ascites in the model in a dose‑dependent manner. Furthermore, EFL2 inhibited tumor cell metastasis and enhanced immune cell infiltration. Meanwhile, EFL2 dose‑dependently downregulated the mRNA and protein expression of NLRP3 and related molecules in the model, and overexpression of NLRP3 abolished these beneficial effects of EFL2. Taken together, the present experimental data suggested that EFL2 has a significant inhibitory effect on ascites of breast cancer liver metastasis in vivo, which may inhibit tumor cell metastasis by downregulating NLRP3 expression, providing an experimental basis for treating breast cancer metastasis.

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