【摘 要】
：
目的：探讨多西他赛与吉非替尼不同时序应对人肿腺癌细胞A549和PC-9生长影响及可能的细胞学机制。方法：qPCR-HRM法检测细胞EGFR和K-ras基因突变；MTT法检测细胞增殖；Western blotting检测细胞EGFR、ERK、AKT、IGF-IR及磷酸化表达,FCM法检测细胞周期.结果：1、A549细胞为EGFR基因野生型,PC-9 细胞为EGFR第19外显子突变型.多西他赛(10-
【机 构】
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Postgraduate Institution of Southern Medical University,Guangzhou 510515,China
【出 处】
：
2012医学科学前沿暨第二届个体化治疗与抗肿瘤药物研究新趋向研讨会
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目的：探讨多西他赛与吉非替尼不同时序应对人肿腺癌细胞A549和PC-9生长影响及可能的细胞学机制。方法：qPCR-HRM法检测细胞EGFR和K-ras基因突变；MTT法检测细胞增殖；Western blotting检测细胞EGFR、ERK、AKT、IGF-IR及磷酸化表达,FCM法检测细胞周期.结果：1、A549细胞为EGFR基因野生型,PC-9 细胞为EGFR第19外显子突变型.多西他赛(10-4M-10-10M)和吉非替尼(A549为10-2M-10-8M； PC-9为10-4M-10-10)呈浓度依赖性抑制A549和PC-9细胞生长.多西他赛和吉非替尼抑制A549及PC-9细胞生长的IC50值分别为5.24×10-7mol/L和2.13x10-8mol/L；1.28×10-5m mol/L和4.58×10-8mol/L.在IC50浓度时,多西他赛序贯吉非替尼对两株细胞生长抑制均具显著增效作用,对A549及PC-9抑制增效率分别为9.34％ (P＜0.05)和8.94％ (P＜0.05),但同时用药只对PC-9细胞具增效作用(增效7.56％,P＜0.05).2、IC50浓度的多西他赛和吉非替尼分别增强和抑制两株细胞EGFR和ERK磷酸化、均抑制PC-9绌胞IGF-1R磷酸化.多西他赛诱导的EGFR和ERK磷酸化显著被序贯应用的吉非替尼抑制.两药同时应用对抑制PC-9细胞的IGF-1R磷酸化具增强作用.3、多西他赛将A549及PC-9细胞阻滞在G2期(分别增加43.28 ％和 30.13％,P＜0.05).吉非替尼对A549无明显的G1期阻滞作用,但将PC-9细胞明显阻滞在G1期(增加29.98％,P＜0.05).结论：多西他赛序贯吉非替尼对抑制EGFR野生型和突变型的A549及PC-9细胞生长均具增效作用,可能与影响细胞EGFR和ERK磷酸化有关.同时应用仅对PC-9细胞具增效作用,可能与IGF-1R磷酸化抑制有关.同时用药或先吉非替尼后多西他赛无增效作用可能与细胞周期相关.结论：多西他赛序贯吉非替尼对抑制EGFR野生型和突变型的A549及PC-9细胞生长均具增效作用，可能与影响细胞EGFR和ERK磷酸化有关。同时应用仅对PC-9细胞具增效作用，可能与IGF-1R磷酸化抑制有关。同时用药或先吉非替尼后多西他赛无增效作用可能与细胞周期相关。
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