γH2AX预测肺癌患者化疗敏感性的研究  

Phosphorylated Histone γH2AX as a Potential Pharmacodynamic Biomarker for Predicting the Sensitivity of Pulmonary Carcinoma to Chemotherapeutic Drugs

作　　者：张贵慧[1] 周萍[1] 董贺[1] 孙青[1] 

机构地区：[1]山东大学附属山东省千佛山医院病理科,济南市250014

出　　处：《中国肿瘤临床》2011年第10期541-544,共4页Chinese Journal of Clinical Oncology

摘　　要：目的:探讨应用磷酸化组蛋白(γH2AX)预测肺癌患者对顺铂、卡铂、吉西他滨、阿霉素等化疗药物敏感性的可行性和可靠性。方法:原代培养肺癌患者肿瘤细胞,分别予不同浓度的化疗药作用后,采用流式细胞术(FCM)、免疫细胞化学法(ICC)、MTT比色法,比较并分析各不同浓度药物作用下肿瘤细胞中γH2AX灶点数、γH2AX阳性细胞百分数及细胞增殖抑制率的差异。结果:在同种药物不同浓度作用下,肿瘤细胞内γH2AX灶点数、γH2AX阳性细胞百分数及细胞增殖抑制率之间的差异具有统计学意义(P均<0.05),并相互之间具有相关性(P均<0.05),不同药物之间γH2AX的表达差异有统计学意义(P均<0.05),并与细胞增殖抑制率间具有相关性(P均<0.05)。结论:肿瘤细胞内γH2AX的表达能在一定程度上预测其对化疗药物的敏感性并对指导肿瘤患者的个体化治疗有重要意义。Objective： To study the feasibility and reliability of using phosphorylated histone H2AX （γH2AX ） as a biomarker for predicting the sensitivity of a pulmonary carcinoma to cisplatin （ DDP ）, carboplatin （ CBP ）, gemcitabine （ GEM ）, and adriamycin （ ADM ）. Methods： Pulmonary carcinoma cells from the patients were primarily cultured and exposed to the above chemotherapeutic drugs at different concentration indices （ CI ）. The proportion of the pulmonary carcinoma cells with positive expression of γH2AX was measured by flow cytometry and immunocytochemistry, whereas cell proliferation was measured with MTT assay. The difference between the number of γH2AX foci, the percentage of the positive cells that expressed and γH2AX, and the inhibitory rate of cell proliferation were analyzed and their correlations were compared. Results： There was correlation between the number of γH2AX foci, the percentage of positive cells expressing γH2AX, and the inhibitory rate of cell proliferation after treatment with different CI of the same drug （ all P 〈 0.05 ）. A correlation was also found among the different drugs （ all P 〈 0.05 ）. Conclusion： Using γH2AX expression for predicting the pharmacodynamic sensitivity of pulmonary carcinoma to chemotherapy agents is feasible and reliable.

关 键 词：组蛋白H2AX 肺肿瘤 原代细胞培养 药物敏感性 

分 类 号：R734.2[医药卫生—肿瘤]