Antitumor effects of morphine and tramadol on lung metastasis of melanoma tumor cells in vitro and in vivo.

Morphine and tramadol are analgesic agents commonly employed in the management of cancer pain. Morphine’s effects on tumor cell growth can be either inhibitory or stimulatory, depending on various factors; however, data regarding tramadol’s impact on melanoma is lacking. The present study aimed to compare the effects of morphine and tramadol on melanoma cells both in vitro and in vivo, to provide further insights into their potential as adjuvant therapeutic agents in melanoma management. Both drugs demonstrated dose-dependent cytotoxicity against B16F10 melanoma cells, achieving a maximum effect of 80% at a concentration of 5.0 μM. Notably, at this concentration, morphine induced greater apoptosis (49%) compared to tramadol (37%). In clonogenic assays, tramadol (0.5 μM) inhibited colony formation by 80%, whereas morphine at the same concentration completely (100%) inhibited colony formation. Both morphine and tramadol significantly reduced the formation of metastases in mice (p < 0.05), with morphine showing a greater reduction in lung tumorigenicity compared to tramadol (p < 0.05). Furthermore, the combination of tramadol at a clinical dose (2.00 μM) with cisplatin (0.0312 μM) enhanced inhibition of cell proliferation compared to cisplatin alone (p < 0.05). In summary, data from in vivo experiments indicated that both drugs induced a significant reduction in tumor size, as well as in the number of metastases. However, morphine was more effective than tramadol. Further research is needed to evaluate antitumor effects of clinical doses of morphine and to explore the potential of tramadol as a substitute for morphine as adjuvant drug in antitumor treatment and pain management of melanoma patients.