• Tadashi Nishiwada, Yoshitaka Kawaraguchi, Keiko Uemura, and Masahiko Kawaguchi.
• Department of Anesthesiology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, Japan. t-nishiwada@naramed-u.ac.jp.
• J Anesth. 2019 Jun 1; 33 (3): 408-415.

PurposeAlthough many oral cancer patients require opioids, the effects of morphine and related drugs on oral cancer progression have not been well established. Thus, we examined the effects of morphine exposure on the viability of human oral squamous carcinoma HSC-3 cells and aimed to identify the underlying mechanism.MethodsWe exposed HSC-3 cells to the various concentrations of morphine (0, 0.1, 1, 10, 100, or 1000 μmol/L) for 48 h and, subsequently, evaluated cell viability using the 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) assay and cytotoxicity using the lactate dehydrogenase (LDH) assay. To explore the effects of morphine on cell proliferation further, colony formation assay and cell cycle analysis were performed. Additionally, the intracellular expression of nuclear factor kappa B (NF-κB) was analyzed using flow cytometry, and vascular endothelial growth factor (VEGF)-A was evaluated using human VEGF assay.ResultsMorphine exposure reduced cell viability and enhanced cytotoxicity in HSC-3 cells in a concentration-dependent manner. The number of colonies in the morphine-treated groups was significantly lower than that in the control group. Consistent with these results, morphine exposure significantly reduced the concentration of VEGF in the cell culture medium in a concentration-dependent manner. However, our data show that morphine at clinical concentrations (0.1-10 μmol/L) does not affect cell cycle and apoptosis.ConclusionsOur results suggest that in human oral cancer HSC-3 cells, morphine exposure inhibits cell viability and growth via suppression of VEGF in clinical conditions.

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