Enhancement of Anticancer Effects by Combining 5-Fluorouracil with Refametinib in Human Oral Squamous Cell Carcinoma Cell Line

(1) Background: Oral squamous cell carcinoma (OSCC) is a significant health burden worldwide. This study aimed to determine the potentials of Refametinib, an orally bioavailable selective MEK1/2 inhibitor, increase effectiveness 5-Fluorouracil (5-FU), common cytotoxic drug, in SCC4 line. (2) Methods: cells were treated with increasing concentrations 5-FU, either alone or combination Refametinib. The chemosensitivity treatment was assessed via viability assay, microscopic observation, colony formation and detection apoptotic markers using Western blotting. whole-cell expression surface programmed death-ligand 1 (PD-L1), immune checkpoint protein which contributes chemoresistance affects response, also determined blotting flow cytometry, respectively. (3) Results: combined suppressed proliferation promoted apoptosis more potent way than 5-FU did. Additionally, MEK/ERK inhibition mitigated 5-FU-induced PD-L1 upregulation. (4) Conclusions: first report enhanced anticancer effect reduced for Refametinib OSCC, suggesting new promising strategy.