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目的:探讨PI3K特异性抑制剂LY294002逆转顺铂耐药口腔鳞癌细胞TCA8113/CDDP的可行性。方法:采用间歇性加药,逐步递增CDDP药量,体外连续诱导培养TCA8113/CDDP细胞;用不同浓度的LY294002和顺铂处理TCA8113和TCA8113/CDDP细胞;MTT法观察对细胞增殖的影响,Western印迹分析LY294002作用前后p-Akt、Akt、PI3K蛋白的表达。结果:建立了舌鳞癌耐药细胞TCA8113/CDDP,耐药指数为7.7;MTT实验显示LY294002对TCA8113和TCA8113/CDDP细胞的抑制作用与浓度及作用时间呈正相关;LY294002联合顺铂对2种细胞的抑制作用比单用顺铂效果好;PI3K、Akt、p-AKT蛋白表达明显降低,其中TCA8113/CDDP细胞中PI3K、AKT、p-AKT蛋白的表达比TCA8113细胞明显增多(P<0.05)。结论:LY294002能增加耐药口腔鳞癌顺铂化疗的敏感性。
Objective: To investigate the feasibility of PI3K-specific inhibitor LY294002 reversing cisplatin-resistant oral squamous cell carcinoma cell line TCA8113 / CDDP. Methods: The dosage of CDDP was gradually increased by intermittent dosing, and the TCA8113 / CDDP cells were induced continuously in vitro. The TCA8113 / CDDP cells were treated with different concentrations of LY294002 and cisplatin. The effects of different doses of CDDP on TCA8113 / CDDP cells were observed. The expression of p-Akt, Akt, PI3K protein before and after LY294002 treatment was analyzed. Results: The drug-resistant cell line TCA8113 / CDDP of tongue squamous cell carcinoma was established and the drug resistance index was 7.7. MTT assay showed that the inhibitory effect of LY294002 on TCA8113 and TCA8113 / CDDP cells was positively correlated with the concentration and duration of action; LY294002 combined with cisplatin (P <0.05). The expression of PI3K, Akt, p-AKT protein in TCA8113 / CDDP cells was significantly higher than that in TCA8113 cells (P <0.05). Conclusion: LY294002 can increase chemosensitivity of cisplatin-resistant oral squamous cell carcinoma.