Enhancing sensitivity to oxaliplatin in tongue squamous cell carcinoma: mechanistic insights and therapeutic potential of DHA combination therapy.

Squamous cell carcinoma of the tongue, a common and aggressive malignancy, poses a substantial threat to health and well-being. Despite the promising results of combination therapy with dihydroartemisinin (DHA) and oxaliplatin (Oxa) in various cancers, its effectiveness in treating tongue squamous cell carcinoma had not been explored prior to this study. Our research found that DHA significantly enhances the sensitivity of tongue squamous cell carcinoma cells to Oxa, even at very low concentrations. The combination treatment was observed to modulate the activity of CDK1 and Cyclin B1, arresting the cell cycle in the G2 phase. Additionally, it reduces mitochondrial membrane potential, prompting the release of cytochrome c and activating cleaved caspase-3, which promotes apoptosis. Notably, surface plasmon resonance and immunoprecipitation experiments revealed that DHA targets and attenuates CDK1 modification, weakening its interaction with STAT3 protein. This leads to reduced expression of anti-apoptotic genes and facilitates programmed cell death in CAL-27 cells. The findings underscore the potential of DHA and Oxa as a potent therapeutic strategy for tongue squamous cell carcinoma, opening avenues for clinical application and further exploration into its mechanistic pathways.