Notch1活化对骨髓瘤细胞株RPMI8226增殖及药物敏感性的影响  

Effect of Notch1 activation on the proliferation and drug sensitivity of RPMI8226 myeloma cells

作　　者：郭冬梅[1] 李玉娟[1] 李纯璞[1] 白观臣[1] 陈晨[1] 滕清良[1] 

机构地区：[1]泰安市中心医院,山东泰安271000

出　　处：《山东医药》2012年第27期14-16,共3页Shandong Medical Journal

基　　金：山东省自然科学基金资助项目(2009ZRA09006);山东省医药卫生科技发展计划项目(2011HW077)

摘　　要：目的观察Notch1信号通路活化与多发性骨髓瘤(MM)发生、发展及耐药的关系,为MM治疗提供新靶点。方法利用携带Notch1-ICN逆转录病毒载体及Notch1-对照病毒(CON)载体感染RPMI8226细胞(分别为病毒组及病毒对照组),同时设未经感染的细胞为未转染组,采用Western blot法检测Notch1-ICN蛋白表达鉴定细胞;采用CCK-8法检测细胞增殖情况及对硼替佐米敏感性的影响;流式细胞术检测细胞周期。结果病毒组Notch1-ICN表达明显上调,约为病毒对照组和未转染组的2.5倍;培养后48、72、96 h病毒组细胞增殖率均显著高于病毒对照组(P均<0.01);随硼替佐米浓度增高,各组细胞抑制作用均逐渐增加,且同浓度条件下病毒组抑制率显著低于病毒对照组及未转染组(P<0.05或0.01);病毒组S期细胞比例明显高于其余两组(P均<0.01)。结论 Notch1信号通路活化与MM的发生、发展及耐药密切相关,有望成为MM治疗的新靶点。Objective To investigate the relationship between Notchl activation and the occurrence, development and drug resistance of multiple myeloma（MM）, so to provide the basis for molecular targeted therapy. Methods Human RP-MI8226 MM cells were infected with Notchl-ICN and Notchl-CON retrovirus stocks （Notchl-ICN group and Notchl-CON group）. RPMI8226 cells without infection were defined as untransfected group. Notchl-ICN protein expression was detec- ted by Western blot analysis. CCK-8 was used to detect the proliferation of MM cells and sensitivity to chemotherapeutic drugs. Cell cycle analysis was detected by flow cytometry. Results The relative expression level of Notchl-ICN protein in Notchl-ICN group increased significantly, and was 2.5 fold higher than that in Notchl-CON group or untransfected group, indicating Notchl signal activation in Notchl-ICN group ; the cell proliferation rates in Notchl-ICN group at 48 h, 72 h and 96 h were all significantly increased as compared with those in Notchl-CON group or untransfected group （P 〈0. 01 ）, and the inhibitory rate was decreased in RPMI8226-1CN cells at 48 h treated by the same concentration of Bortezomib （ P 〈 0.05 or 0.01 ） ; S phase cells in Notchl-ICN group were increased as compared with that in Notchl-CON group or untransfected group （P 〈 0. 05）. Conclusion Notchl activation was closely correlated with the occurrence, development and drug re-sistance of MM ; Notchl signaling is promising to be used as a new target for MM treatment.

关 键 词：NOTCH通路 多发性骨髓瘤 细胞周期 药物敏感性 

分 类 号：R733.3[医药卫生—肿瘤]