MBD4通过调控DNA错配修复逆转口腔鳞状细胞癌的顺铂耐药性

doi:10.13701/j.cnki.kqyxyj.2026.06.006

摘要/Abstract

摘要： 目的:研究DNA糖基化酶MBD4在顺铂耐药性的口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)细胞中表达并探究其临床意义。方法:以OSCC顺铂耐药细胞株CAL27/DDP和亲本细胞株CAL27作为研究对象。各浓度顺铂梯度处理两种细胞系,Cell Counting Kit-8(CCK-8)法测其IC₅₀值。利用Western blot及实时定量聚合酶链反应(real-time quantitative polymerase chain reaction,RT-qPCR)验证两种细胞系中相关蛋白及mRNA的表达差异。利用质粒转染构建稳定的OSCC耐药细胞MBD4过表达细胞系。运用CCK-8实验、细胞划痕实验及细胞体外侵袭迁移实验(Transwell)检测各细胞系在顺铂环境中的存活率及迁移、侵袭能力的变化。结果:Western blot及RT-qPCR结果显示,相较于亲本细胞系,MBD4以及错配修复相关蛋白MLH1、MSH2、MSH6、PMS2在OSCC顺铂耐药细胞系中低表达(P<0.01)。过表达MBD4后,耐药细胞株在顺铂环境中的生存率降低(P<0.001),且其侵袭、迁移能力减弱(P<0.001),恢复了对于顺铂的敏感性,同时耐药细胞中错配修复相关蛋白的表达显著升高(P<0.001)。结论:DNA糖基化酶MBD4与OSCC的顺铂耐药性密切相关,过表达MBD4可以逆转OSCC细胞产生的顺铂耐药性,这种逆转作用与耐药细胞株中的DNA错配修复功能有关。

关键词: 口腔鳞状细胞癌, 顺铂, 化疗耐药, DNA错配修复

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

张义晗, 李吉辰. MBD4通过调控DNA错配修复逆转口腔鳞状细胞癌的顺铂耐药性[J]. 口腔医学研究, 2026, 42(6): 493-499.

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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