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

• Published in: Clinical & experimental metastasis 2023-04, Vol.40 (2), p.149-160
• Main Authors: Xu, Sunmian, Li, Xiaohui, Li, Wenbin, Ma, Nina, Ma, Hongjun, Cui, Jian, You, Xiaogang, Chen, Xuexin
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Assaying; Biomedical and Life Sciences; Biomedicine; Breast cancer; Breast Neoplasms - pathology; Cancer Research; Cell cycle; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement; Cell Proliferation; Cholecystokinin; Cyclin D1; Cyclooxygenase-2; E-cadherin; Epithelial-Mesenchymal Transition; ErbB-2 protein; Female; Flow cytometry; G1 phase; Gelatinase B; Growth factors; Hematology; Humans; Matrix metalloproteinase; Matrix metalloproteinases; Metalloproteinase; Metastases; Metastasis; Mice; N-Cadherin; Oncology; Proteins; Research Paper; Sodium; Sufentanil; Sufentanil - pharmacology; Surgical Oncology; Transplantation; Tumors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A; Vimentin
• ISSN: 0262-0898; 1573-7276
• DOI: 10.1007/s10585-023-10199-6

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.