Synergistic inhibition of proliferation and induction of apoptosis in oral tongue squamous cell carcinoma by mebendazole and paclitaxel via PI3K/AKT pathway mitigation.

Serve as one of common cancer in the mouth, oral tongue squamous cell carcinoma (OTSCC) is a serious problem affecting human oral health. The aim of this study was to evaluate the effects of mebendazole (MBZ) alone and combined with paclitaxel on the proliferation and occurrence of OTSCC and its molecular mechanism. Cell viability, apoptosis, cell cycle distribution, and the expression of PI3K, p-PI3K, AKT, and p-AKT were evaluated by Cell Counting Kit-8 (CCK-8), flow cytometry, and Western blot, respectively. Immunofluorescence was used to assess changes in microtubule morphology of CAL-27 and UM-SCC-1 cells with alpha-tubulin antibody labeling. The CCK-8 assay revealed a dose-dependent inhibitory effect of both MBZ and paclitaxel on CAL-27 and UM-SCC-1 cells. The apoptosis assay showed significantly elevated levels of apoptosis-specific markers, cleaved caspase-3, and cleaved PARP, in the combined treatment group compared to the control and single-agent groups. The combination of MBZ and paclitaxel showed enhanced inhibition of key PI3K/AKT pathway proteins' phosphorylation and reduced expression of Cyclin B and PCNA compared to the control. The alpha-tubulin staining area was notably reduced in the combined treatment group relative to the other groups. Both MBZ and paclitaxel treatments inhibited of cell proliferation and microtubule formation by reducing the PI3K/AKT pathway in CAL-27 and UM-SCC-1 cells, with the combination demonstrating synergistic effects. Our study suggests MBZ and paclitaxel as potential agents for the treatment of OTSCC.