酪氨酸代谢物对肺癌细胞增殖、周期及化疗药物敏感性的影响  

Effect of tyrosine metabolites on cell proliferation,cell cycle and chemosensitivity of lung cancer cells

作　　者：李洁[1] 赵珂[1] 孔祥祯[2] 詹轶群[1] 杨晓明[1,2] 李长燕[1] 

机构地区：[1]军事医学科学院放射与辐射医学研究所,北京100850 [2]天津大学,天津300072

出　　处：《军事医学》2017年第6期487-493,共7页Military Medical Sciences

基　　金：国家自然科学基金资助项目(81472586);国家"973"计划资助项目(2014CBA02001)

摘　　要：目的探讨4种酪氨酸代谢物对肺癌细胞增殖、周期及化疗药物敏感性的影响。方法不同浓度的酪氨酸代谢物——酪氨酸、4-羟苯丙酮酸(HPPA)、尿黑酸(HGA)、延胡索酸(FA)分别处理A549细胞,通过高内涵实时监测肺癌细胞的增殖,流式细胞仪检测肺癌细胞周期的变化及对化疗药物的敏感性,Western印迹检测凋亡相关蛋白Bcl-2、Bax的表达。结果 4种酪氨酸代谢物对A549细胞的增殖及周期均无影响。HGA可降低吉非替尼(Gefitinib)诱导的A549细胞凋亡,抑制Bax表达,同时上调Bcl-2的表达水平;FA则可增加其诱导的A549细胞凋亡,促进Bax表达,同时下调Bcl-2的表达水平。酪氨酸和HPPA对Gefitinib诱导的细胞凋亡均无明显影响。结论HGA与FA可调节肺癌细胞化疗药物的敏感性,揭示了酪氨酸代谢通路对肺癌细胞的调控作用,为肿瘤代谢异常的研究奠定了基础。Objective To investigate the effects of four tyrosine metabolites on the proliferation,cell cycle and chemosensitivity of lung cancer cells. Methods A549 cells were cultured with different concentrations of tyrosine metabolites： tyrosine,4-hydroxyphenylpyruvate（ HPPA）,homogentisic acid（ HGA） and fumaric acid（ FA） in vitro. High content imaging analysis system was used to monitor cell proliferation. Flow cytometry was used to detect cell cycle and apoptosis. Protein and mRNA level of Bax and Bcl-2 were measured by Western blot. Results Tyrosine metabolites had no effect on cell cycle and proliferation of A549 cells. HGA decreased the cell apoptosis of A549 cells induced by Gefitinib with depressed Bax expression and elevated Bcl-2 expression. However,FA increased the apoptosis of A549 cells induced by Gefitinib with up-regulation of Bax and down-regulation of Bcl-2. No obvious effect of tyrosine and HPPA was detected on Gefitinib induced cell apoptosis. Conclusion HGA and FA may play an important role in drug sensitivity of lung cancer cells,indicating a critical role of tyrosine metabolism in lung cancer.

关 键 词：肺肿瘤 酪氨酸代谢物 细胞周期 细胞增殖 细胞凋亡 药物敏感性 

分 类 号：R734.2[医药卫生—肿瘤]