P13K／AKT信号转导通路与人舌鳞癌细胞TCA8113顺铂耐药的相关性研究

目的：探讨P13K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、P13K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；P13K、Akt、P—AKT蛋白表达明显降低，其中TCA8113／CDDP细胞中P13K、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。

Study on the Relationships Between PI3K/Akt Signaling Transduction Pathway and Cisplatin Resistance of TCA8113 Tongue Cancer Cell Lines

Objective： To discuss the effect of PI3K/AKT pathway inhibitor LY294002 on the proliferation of TCA8113, TCA8113/CDDP cells and to study the relationship between signaling transduction pathway and cisplatin resistenee. Methods： The concentration of CDDP added to TCA8113 cells was increased gradually and the chemotherapeutic drug was added continually, which was to induce the CDDP-resistance in TCA8113 cells. The TCA8113 and TCA8113/CDDP cell lines were treated with different concentration of LY294002 and cisplatin. The inhibition rate of LY294002 and cisplatin for TCA8113 cells and TCA8113/CDDP cell lines were determined by MTT assay. The expression results of PI3K, p-AKT, AKT were detected by Western blot. Results： The TCA8113/ CDDP cells was established and the cells＇ drug resistence ability was 7.7. The LY294002 and cisplatin inhibition rate of TCA8113 and TCA8113/CDDP cells were time and dose-dependent, the combination of LY294002 and CD- DP exerted a synergistic effect on both cell lines growth in hibition. Moreover, the expression of p-AKT, AKT and PI3K were obviousely decreased. The expression of PI3K, AKT and p-AKT in TCA8113/CDDP cells was more than that in TCA8113. Conclusion： LY294002 could induce TCA8113 and TCA8113/CDDP cells sensitivity to CDDP and inhibit the proliferation of TCA8113 and TCA8113/CDDP cells.