Abstract
Background/Aim: The serine/threonine-protein kinase B-Raf (BRAF) V600E mutant (BRAFV600E) inhibitor vemurafenib, has improved clinical outcomes for patients with BRAFV600E melanoma, but acquired cellular resistance mediated by AKT serine/threonine kinase 1 (AKT) phosphorylation limits its efficacy. We examined the effect of resveratrol on vemurafenib-resistant melanoma cells. Materials and Methods: A vemurafenib-resistant human metastatic melanoma cell line positive for the BRAF V600E mutation was established. The anti-tumorigenic effects of vemurafenib and resveratrol, both alone and in combination, were examined through analysis of cell proliferation and protein expression. Results: The level of phosphorylated AKT (p-AKT) was increased in the primary melanoma cells after treatment with vemurafenib, and the basal level of p-AKT was increased in vemurafenib-resistant melanoma cells. Notably, resveratrol both alone and in combination with vemurafenib effectively suppressed cell proliferation and AKT phosphorylation in both parental and vemurafenib-resistant melanoma cells. Conclusion: Vemurafenib resistance can be reversed by addition of resveratrol in patients undergoing treatment with BRAF inhibitors.
- Received April 5, 2016.
- Revision received May 16, 2016.
- Accepted May 17, 2016.
- Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved