PI-103对多药耐药白血病细胞体外作用的研究(3)
2015-06-16 01:07
导读：仅在实验前2周开始撤除阿霉素培养，因而，该细胞在2g/ml阿霉素作用下是不会死亡的，只是细胞的生长速度减慢了，细胞并未发生凋亡。联用PI-103后，尽管
仅在实验前2周开始撤除阿霉素培养，因而，该细胞在2μg/ml阿霉素作用下是不会死亡的，只是细胞的生长速度减慢了，细胞并未发生凋亡。联用PI-103后，尽管K562/A02细胞的生长受抑率仅仅是两药的叠加，但细胞凋亡是否有增加，尚不明确，换用流式细胞术检测细胞凋亡率也许有助于得出更确切的结论。其次，是否有其他耐药机制的参与，拮抗了细胞内阿霉素浓度提高所致的杀细胞效应，尚有待进一步的研究。第三，与K562/A02细胞的特性有关。Kojima等[7]发现，在野生型P53存在的白血病细胞中，PI-103与阿霉素有协同作用，而在P53突变的白血病细胞，则无协同效果。以往研究显示，K562细胞存在P53突变，因而，PI-103和阿霉素在K562及其耐药株K562/A02中无协同杀伤白血病细胞的作用。然而，多数白血病原代细胞不存在P53突变。因而，体内应用于病人时，PI-103可能会与阿霉素产生协同效应。
总之，在体外，PI-103具有抗白血病细胞作用，对敏感和耐药细胞同样有效；它能增加细胞内阿霉素浓度，增加细胞对阿霉素的敏感性。双效PI3K/AKT/mTOR抑制剂是一种有良好应用前景的药物，对PI-103的深入研究，必将为开发研制新的双效PI3K/AKT/mTOR抑制剂奠定坚实的基础。
参 考 文 献
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