MBD4 Reverses Cisplatin Resistance in Oral Squamous Cell Carcinoma by Regulating DNA Mismatch Repair

doi:10.13701/j.cnki.kqyxyj.2026.06.006

Abstract

Abstract: Objective: To investigate the expression of DNA glycosylation enzyme MBD4 in oral squamous cell carcinoma (OSCC) cells with cisplatin resistance and explore its clinical significance. Methods: Cisplatin resistant cell lines (CAL27/DDP) and parental cell lines (CAL27) were used as the research subjects in oral squamous cell carcinoma. Two cell lines were treated with cisplatin at various concentration gradients, and their IC50 values were measured using the cell counting kit-8 (CCK-8) method. Western blotting and real-time quantitative polymerase chain reaction (RT-qPCR) were used to verify the differential expression of relevant proteins in two cell lines. MBD4 overexpression cell line was constructed in oral squamous cell carcinoma resistant cells using plasmid transfection. CCK-8 assay, cell scratch assay, and cell invasion and migration experiment were used in vitro (Transwell) to detect the changes in survival rate, migration, and invasion ability of various cell lines in cisplatin environment. Results: Western blotting and RT qPCR results showed that compared with the parental cell line, MBD4 and mismatch repair related proteins MLH1, MSH2, MSH6, and PMS2 were lowly expressed in cisplatin resistant oral squamous cell carcinoma cell lines (P<0.01). After overexpression of MBD4, the survival rate of drug-resistant cell lines in cisplatin environment was significantly reduced (P<0.001), and their invasion and migration abilities were greatly weakened (P<0.001), restoring sensitivity to cisplatin. At the same time, the expression of mismatch repair related proteins in drug-resistant cells was significantly increased (P<0.001). Conclusion: DNA glycosylation enzyme MBD4 is closely related to cisplatin resistance in OSCC. Overexpression of MBD4 can reverse cisplatin resistance in OSCC cells, and this reversal effect is related to the DNA mismatch repair function in drug-resistant cell lines.

Key words: oral squamous cell carcinoma, cisplatin, chemotherapy resistance, DNA damage repair

ZHANG Yihan, LI Jichen. MBD4 Reverses Cisplatin Resistance in Oral Squamous Cell Carcinoma by Regulating DNA Mismatch Repair[J]. Journal of Oral Science Research, 2026, 42(6): 493-499.

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