Gamof Treats Drugresistant Oral Squamous Cell Carcinoma By Inducing Ferroptosis

Oral squamous cell carcinoma (OSCC) is one of the most common malignancies in the head and neck region, characterized by high recurrence and metastasis rates. Although surgery is the primary treatment, chemotherapy remains an important adjuvant therapy for advanced or recurrent patients. However, the chemotherapeutic efficacy of doxorubicin (DOX) is significantly limited due to drug resistance in tumor cells. Resistance mechanisms include the formation of a “ROS barrier” by enhancing the antioxidant system in tumor cells, regulating iron metabolism homeostasis, and overexpressing drug efflux pumps (such as P-glycoprotein), which greatly reduce drug effectiveness. In this study, we designed and synthesized a gallium-based metal-organic framework (GaMOF) and tested its effects on drug-resistant OSCC by examining key indicators of ferroptosis. GaMOF was found to increase the levels of reactive oxygen species (ROS) in tumor cells, disrupt redox balance, and induce ferroptosis by interfering with iron metabolism homeostasis and promoting lipid peroxidation. Additionally, GaMOF significantly increased DOX accumulation in drug-resistant tumor cells, overcoming the efflux barrier. The study demonstrated that GaMOF outperformed DOX or MOF alone in treating DOX-resistant OSCC cells, highlighting the advantages of multi-mechanistic synergy in reversing drug tolerance. This research provides an innovative multi-functional therapeutic strategy to address chemoresistance in OSCC and showcases the potential application of GaMOF in precision cancer therapy, offering theoretical support and practical evidence for the treatment of refractory tumors in the future.