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

Abstract

Background: Cancer 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. Methods: MTT 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. Results: Nalbuphine 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. Conclusions: Our 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.