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Sufentanil combined with parecoxib sodium inhibits proliferation and metastasis of HER2-positive breast cancer cells and regulates epithelial-mesenchymal transition

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Abstract

Background

Sufentanil combined with parecoxib sodium is a commonly used postoperative medication for cancer patients. However, the effects of this combination therapy on human epidermal growth factor receptor-2 (HER2)-positive breast cancer cells have still remained elusive. This study aimed to investigate the effects and potential mechanisms of sufentanil combined with parecoxib sodium on HER2-positive breast cancer cells.

Methods

The cell counting kit-8 (CCK-8), colony formation, flow cytometry, scratch, transwell invasion, and angiogenesis assays were used to assess the proliferation, cell cycling, migration, invasion, and angiogenesis of HER2-positive breast cancer BT474 cells. Western blot assay was employed for detecting the expression levels of proteins involved in the cell cycle, migration, invasion, angiogenesis, and epithelial-mesenchymal transition (EMT). The in vivo effects of tumor growth and metastasis were examined by establishing an orthotopic transplantation mouse model of HER2-positive breast cancer (MMTV-PyMT).

Results

Functional assays indicated that sufentanil combined with parecoxib sodium induced blockade of HER2-positive breast cancer BT474 cells in the G1 phase of the cell cycle and inhibited cell proliferation, migration, angiogenesis, and invasion in vitro. Western blot assay revealed that sufentanil combined with parecoxib sodium downregulated the expression levels of cyclin D1, matrix metalloproteinase-9 (MMP-9), cyclooxygenase-2 (COX-2), vascular endothelial growth factor A (VEGFA), and EMT-related proteins (N-cadherin, Vimentin, and Snail), while up-regulated the expression level of E-cadherin in BT474 cells. In addition, it was found that sufentanil combined with parecoxib sodium inhibited tumor growth and metastasis in the orthotopic transplantation mouse model of HER2-positive breast cancer.

Conclusion

Sufentanil combined with parecoxib sodium inhibited HER2-positive breast cancer progression, including cell proliferation, cell cycle, migration, invasion, and angiogenesis, and regulated EMT.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This study was financially supported by the Natural Science Foundation of Ningxia Province (Grant No. 2021AAC03399). The funding agency was not involved in the design of the study and collection, analysis, and interpretation of data, and in writing the manuscript.

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Authors and Affiliations

  1. School of Clinical Medicine, Ningxia Medical University, 750004, Yinchuan, China

    Sunmian Xu

  2. Huashan Hospital, Fudan University, 200040, Shanghai, China

    Sunmian Xu

  3. General Hospital of Ningxia Medical University, 750004, Yinchuan, China

    Xiaohui Li, Wenbin Li, Nina Ma, Hongjun Ma, Jian Cui, Xiaogang You & Xuexin Chen

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Correspondence to Xuexin Chen.

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Xu, S., Li, X., Li, W. et al. Sufentanil combined with parecoxib sodium inhibits proliferation and metastasis of HER2-positive breast cancer cells and regulates epithelial-mesenchymal transition. Clin Exp Metastasis 40, 149–160 (2023). https://doi.org/10.1007/s10585-023-10199-6

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