Nalbuphine suppresses breast cancer stem-like properties and epithelial-mesenchymal transition via the AKT-NFκB signaling pathway

Journal of Experimental & Clinical Cancer Research

Yuanyuan Luo¹  Qingping Wen²  Jiachuan Yu³ 

[1] 0000 0000 9558 1426, grid.411971.b, Institute of Cancer Stem Cell, Dalian Medical University, 116044, Dalian, China;grid.452435.1, Department of Anesthesiology, The First Affiliated Hospital of Dalian Medical University, Zhongshan Road, 116011, Dalian, China;grid.452435.1, Department of Anesthesiology, The First Affiliated Hospital of Dalian Medical University, Zhongshan Road, 116011, Dalian, China;0000 0000 9558 1426, grid.411971.b, Institute of Cancer Stem Cell, Dalian Medical University, 116044, Dalian, China;

关键词: Nalbuphine;    Breast cancer;    Stem-like traits;    Epithelial-mesenchymal transition;    AKT-NFκB pathway;   

DOI  :  10.1186/s13046-019-1184-1

来源: publisher

【 摘 要 】

BackgroundCancer pain is a debilitating disorder of human breast cancer and a primary determinant of the poor quality of life, and relieving pain is fundamental strategy in the cancer treatment. However, opioid analgesics, like morphine and fentanyl, which are widely used in cancer pain treatment have been reported to enhance stem-like traits and epithelial-mesenchymal transition (EMT) of breast cancer cells. As such, it is vital to make the best choice of analgesic for breast cancer management.MethodsMTT assays and colony formation assays were performed to examine tumor cell proliferation upon nalbuphine treatment. RT-PCR, western blot, flow cytometry, sphere formation, immunohistochemistry, transwell assays, wound healing assays and mouse xenograft were used to assess the biological effects of nalbuphine treatment.ResultsNalbuphine inhibited breast cancer cell growth and tumorigenesis, with little effect on noncancerous breast cell lines. Nalbuphine suppressed cancer stem-like traits and EMT in both breast cancer cells and mouse xenograft tumor tissues. Additionally, activation of AKT reversed the nalbuphine-induced inhibition of cancer stem-like properties, tumorigenesis and EMT.ConclusionsOur results demonstrate a new role of nalbuphine in inhibiting cancer stem-like properties and EMT in addition to relieving pain, which suggests that nalbuphine may be effective in breast cancer treatment.

【 授权许可】

CC BY