Inhibitory activity of acteoside in melanoma via regulation of the ERβ-Ras/Raf1-STAT3 pathway

Melanoma is an aggressive cancer with a rapidly increasing incidence rate worldwide. Acteoside has been shown to have antitumor effects in multiple human cancers; however, the underlying function and mechanisms of acteoside in melanoma remain unclear. This study explored the inhibitory effect of acteoside on melanoma and the possible mechanisms. Acteoside (15 mg/kg, 30 mg/kg) was administered to mice daily for 21 days. ICI182,780 (0.5 mg/kg) was intraperitoneally injected 30 min before acteoside administration three times a week to evaluate whether the effects elicited by acteoside were mediated via the estrogen receptor. Tumor growth and metabolism, cardiac function, ROS and apoptosis levels in the spleen, serum inflammatory factors, and immune cells in the spleen were monitored. STAT3, p-STAT3, CD31, and survivin levels in tumor tissues were measured via immunofluorescence. Ras, Raf1, STAT3, p-STAT3, Bcl-2, Bax, cleaved caspase-3, and cleaved caspase-9 levels in tumor tissues were determined via Western Blotting. The results showed that acteoside inhibited melanoma growth, alleviated inflammation levels in mice, attenuated ROS and apoptosis levels in the spleen, downregulated the levels of CD31, survivin, Ras, Raf1, p-STAT3, and Bcl-2, and upregulated the levels of ERβ, Bax, cleaved caspase-3, and cleaved caspase-9. Moreover, the effect of acteoside was blocked by ICI182,780. Acteoside may promote the apoptosis of tumor cells by regulating the ERβ-Ras/Raf1-STAT3 signaling axis, thus inhibiting the occurrence and development of melanoma.