抑制磷酸腺苷激活的蛋白激酶活性增强人鼻咽癌细胞放射敏感性  

Suppression of Amp activated protein kinase activity enhance the radiosensitivity of human nasopharyngeal carcinoma cells

作　　者：卢小迪[1,2] 朱小东[1,2] 赵伟[1,2] 曲颂[1,2] 梁霞[1,2] 苏芳[1,2] 马慧[1,2] 

机构地区：[1]广西医科大学附属肿瘤医院 [2]广西壮族自治区肿瘤研究所放疗科,南宁530021

出　　处：《重庆医学》2014年第22期2900-2902,共3页Chongqing medicine

基　　金：国家自然科学基金资助项目(81160285);广西壮族自治区自然科学基金资助项目(桂科自2010gxnsfa013240);2012年广西研究生创新计划项目(YCBZ2012017)

摘　　要：目的研究磷酸腺苷激活的蛋白激酶(AMPK)活化程度对人鼻咽癌(NPC)细胞放射敏感性的影响。方法应用AMPK活化抑制剂Compound C(CC)处理人NPC CNE-2细胞1h后,给予X线照射,48h后Western blot检测总AMPK(tAMPK)、磷酸化AMPK(p-AMPK)及自噬标志物MAPlLC3的变化;透射电子显微镜检测自噬小体形成情况。经不同药物干预后的CNE-2细胞给予X线照射48h后四甲基偶氮唑盐(MTT)和流式细胞技术检测两组细胞活力和凋亡变化。结果 CNE-2细胞经CC干预后t-AMPK未发生明显变化(P>0.05),而活化状态的AMPK,即p-AMPK表达显著降低(P<0.01),且自噬标志物MAPlLC3的表达量显著降低(P<0.05),自噬小体数量明显减少(P<0.05);CNE-2细胞经CC干预后进行X线照射可明显抑制其增殖并促进细胞凋亡(P<0.05)。结论 CC可通过抑制细胞自噬来增强放射线对NPC CNE-2细胞增殖抑制和凋亡促进作用,从而增强NPC的放射敏感性。Objective To investigate the effect of Amp activated protein kinase（AMPK）activity in radiosensitivity of human na-sopharyngeal carcinoma cells .Methods Human nasopharyngeal carcinoma cells ,CNE-2 ,were treated with AMPK inhibitor ,Com-pound C（CC） ,for 1 h .Then cells were explored in X-ray .The expression of total AMPK （t-AMPK） ,phosphorylation AMPK （p-AMPK） ,and MAPlLC3 were detected by Western blot .The number of autophagosomes were observed and calculated by transmis-sion electron microscope（TEM） .Cells processed with CC were explored in X-ray .MTT assay was used to detect the difference of two groups in cell proliferation .Cell apoptosis were assayed by flow cytometry .Results The expression of p-AMPK in CC group cells were significantly downregulated compared to the negative control group cells （P〈 0 .01） ,while no significant change of t-AMPK expression were found（P〉0 .05） .The expression of MAPlLC3 and the number of autophagosomes in CC group cells were significantly decreased compared to the control group cells （P〈0 .05） .Correspondingly ,the cell proliferation rate in CC group was lower than in control group ,and the percent of apoptosis cells was higher in CC group than in control group （P〈0 .05） .Conclusion Suppression of AM PK activity could inhibited autophagy induced by decreasing the degree of p-AM PK ,then enhanced the effect of proliferation inhibition and apoptosis promotion in CNE-2 cells .The AMPK inhibitor ,CC ,can serve as an effective assistant treatment of radiotherapy for nasopharyngeal carcinoma .

关 键 词：抑制剂 鼻咽癌 放射敏感性 自噬 

分 类 号：R739.63[医药卫生—肿瘤]