TY - JOUR T1 - Effect of Metformin in Combination With Trametinib and Paclitaxel on Cell Survival and Metastasis in Melanoma Cells JF - Anticancer Research JO - Anticancer Res SP - 1387 LP - 1399 DO - 10.21873/anticanres.14896 VL - 41 IS - 3 AU - YOUNGKI LEE AU - DEOKBAE PARK Y1 - 2021/03/01 UR - http://ar.iiarjournals.org/content/41/3/1387.abstract N2 - Background/Aim: Despite clinical benefit from treatment with dabrafenib and trametinib in melanoma patients with BRAF mutations, half relapse within months and one-third are unresponsive to treatment. We evaluated the anticancer potential of metformin in combination with trametinib plus paclitaxel, against four melanoma cell lines. Materials and Methods: Metformin with trametinib and paclitaxel was tested for effects on cell viability, signaling molecules in MAPK and mTOR pathways, factors involved in epithelial-mesenchymal transition (EMT), and cell motility. Results: The combination of metformin with trametinib and paclitaxel showed differential growth inhibitory effects; synergistic effects were observed in a cell line in which metformin suppresses ERK activity, whereas the combination showed antagonistic effects in a cell line with metformin-induced ERK activation. Trametinib or paclitaxel increased the expression of EMT regulators and melanoma cell motility, which were suppressed by combining metformin with trametinib and paclitaxel. Conclusion: The combined treatment of metformin with trametinib and paclitaxel showed divergent effects on melanoma cell viability. Metformin might be useful as a potential adjuvant against cell proliferation and metastatic activity in melanoma patients. ER -