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作 者:齐长娥 李德超[1] 朱杨[1] 姚丛姗 Hussein Helal 赵艳宇[1]
机构地区:[1]佳木斯大学附属口腔医院口腔种植科,黑龙江佳木斯154004
出 处:《生物技术通讯》2014年第3期373-376,共4页Letters in Biotechnology
基 金:黑龙江省自然科学基金(D2010-25);黑龙江省人事厅项目(2009-23);黑龙江省卫生厅课题(2013218)
摘 要: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 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.
关 键 词:P13IGAkt信号转导通路 LY294002 口腔鳞状细胞癌 顺铂 耐药
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