Notch信号抑制剂（2S）-N—N-（3，5-二氟苯乙酰基）-L-丙氨酰-2-苯基甘氨酸叔丁酯对肾正常及肿瘤细胞c—myc的影响  

Contribution of Notch signaling inhibitor N-[ N-（ 3, 5-difluorophenacetyl ） -L-alanyl ] -S-phenylg- lycine t-butylester to c-myc expression and its functions in kidney normal and cancer cells

作　　者：黄庆波[1] 艾青[1] 刘尚文[1] 朱鸣阳[1] 马鑫[1] 张旭[1] 

机构地区：[1]解放军总医院泌尿外科,北京100853

出　　处：《中华实验外科杂志》2012年第5期924-926,共3页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目（30972982）

摘　　要：目的观察Notch信号抑制剂（2s）-N—N-（3，5-二氟苯乙酰基）-L-丙氨酰-2-苯基甘氨酸叔丁酯（DAPT）对肾小管上皮细胞HKC及肾肿瘤细胞786-O中c—myc表达及对细胞增殖的影响。方法通过实时定量聚合酶链反应（real—timePCR）及Westernblot方法连续3次检测HKC及786-O中c—myc的表达及DAPT处理后HKC及786—0细胞中c—myc的表达变化，并检测DAPT对细胞增殖及周期的影响。结果786-O中c—myc表达比HKC高（2．54±0．24）倍（P〈0．01）。DAPT处理后，HKC及786．0细胞中c．myc表达分别下调（1．41±0．13）和（2．93±0．26）倍（P均〈0．05）；两株细胞的增殖均受到抑制，HKC及786-O G0／G1期细胞比例分别增加9．75％和16．54％（P均〈0．01）。结论Notch信号抑制剂DAPT可能通过抑制c-myc的表达而抑制肾正常及肿瘤细胞的增殖。Objective To investigate the contribution of Notch signaling inhibitor N-[ N-（ 3, 5-di- fluorophenacetyl）-L-alanyl ]-S-phenylglycine t-butylester （DAPT） to c-myc expression and determine its functions in human kidney tubule epithelial cell line HKC and renal cell carcinoma （RCC） cell line 786-0. Methods Basal expression of c-myc in HKC and 786-0 cells and that of e-myc in cells with or without DAPT treatments were detected by using triplicate real-time polymerase chain reaction （PCR） and Western blotting. Furthermore, proliferation and cell cycle assays were performed on these cells. Results e-mye was upregulated in 786-0 ceils relative to HKC （ 2. 54±0. 24 folds, P 〈 0. 01 ）. After DAPT treatments, e-myc expression in 786-0 and HKC cells were both downregulated （2. 93 ±0. 26 folds, and 1.41±0. 13 folds, respectively, both P 〈 0.05 ）; Cell proliferation was attenuated and cell cycles were arrested at G0/G1 phase （ 16. 54% in 786-0 cells and 9.75% in HKC cells, respectively, both P 〈0. 01 ）. Conclusion Notch pathway signaling is associated with kidney normal and cancer cells proliferation and e-myc may serve as a target gene.

关 键 词：NOTCH γ内分泌酶 C-MYC 肾肿瘤 

分 类 号：R737.11[医药卫生—肿瘤]