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[目的]探讨Akt抑制剂MK2206对三阴性乳腺癌顺铂耐药细胞株MDA-MB-231/DDP生长活性及耐药性的影响。[方法 ]使用不同浓度梯度的顺铂(DDP)、MK2206单药或联合作用于MDA-MB-231/DDP细胞,MTT法检测各药物对细胞的增殖抑制率;高效液相色谱法检测细胞内DDP药物浓度的改变;Western Blot、Real-time PCR分别检测细胞内Akt蛋白及MDR相关基因(MDR1、BCRP、MMP7、GST-π)的表达水平。[结果]MK2206单药对MDAMB-231/DDP细胞有明显的抑制作用,无毒剂量的MK2206可明显增强MDA-MB-231/DDP细胞对顺铂的敏感性,增加细胞内顺铂浓度,使细胞内Akt蛋白及MDR相关基因(MDR1、BCRP、MMP7、GST-π)的表达水平明显降低。[结论 ]MDA-MB-231/DDP细胞的顺铂耐药性与细胞内Akt蛋白的过度表达有关,MK2206有明显的顺铂增敏作用,能部分逆转MDA-MB-231/DDP细胞对顺铂的耐药性,其机制可能与降低细胞内MDR1、BCRP、MMP7、GST-π的基因表达水平有关。
[Objective] To investigate the effect of Akt inhibitor MK2206 on the growth activity and drug resistance of cisplatin-resistant cell line MDA-MB-231 / DDP in triple negative breast cancer. [Methods] The proliferation of MDA-MB-231 / DDP cells was induced by different concentrations of cisplatin (DDP) and MK2206 alone or in combination with MTT method. The intracellular DDP drug concentration. The expression of Akt protein and MDR related genes (MDR1, BCRP, MMP7, GST-π) were detected by Western Blot and Real-time PCR respectively. [Results] MK2206 alone had a significant inhibitory effect on MDAMB-231 / DDP cells. The non-toxic dose of MK2206 significantly increased the sensitivity of cisplatin to MDA-MB-231 / DDP cells and increased the intracellular cisplatin concentrations The expression levels of Akt and MDR related genes (MDR1, BCRP, MMP7, GST-π) in the cells were significantly decreased. [Conclusion] The cisplatin resistance of MDA-MB-231 / DDP cells is related to the overexpression of intracellular Akt protein. MK2206 has a significant cisplatin-sensitizing effect and partially reverses the inhibitory effect of cisplatin on MDA-MB-231 / The mechanism of resistance to platinum may be related to the decrease of gene expression of MDR1, BCRP, MMP7 and GST-π in cells.