CAJ | 학술논문

目的：探讨 Src 酪氨酸激酶抑制剂Ⅱ对 Src 蛋白及其下游信号作用。方法采用半定量 RT-PCR 法检测 Src 酪氨酸激酶抑制剂Ⅱ处理后的人膀胱癌细胞 T24各浓度组（0、0．2、1．0、5．0μmol／mL 组）的 c-Src、p38MAPK 基因表达的变化情况，使用 Western blot 检测 Src 酪氨酸激酶抑制剂Ⅱ处理后 T24细胞内的 c-Src 蛋白磷酸化类型与非磷酸化类型的表达情况。结果Src 酪氨酸激酶抑制剂Ⅱ处理有下调后的人膀胱癌细胞 T24各浓度组的 c-Src mRNA 的表达下调；p38基因的表达呈逐渐下调趋势。处理后 T24细胞内 c-Src 基因在蛋白表达水平上其磷酸化类型随 Src 酪氨酸激酶抑制剂Ⅱ浓度的增高表达逐渐下降，并且呈剂量效应关系。结论Src 酪氨酸激酶抑制剂Ⅱ可能通过竞争 Src 蛋白磷酸化位点，使其不能激活，导致下游的细胞传导途径失活使得 T24细胞增殖得到抑制，认为 Src 蛋白具有作为膀胱移行细胞癌分子靶向治疗的潜在靶点的可能性。Src 酪氨酸激酶抑制剂Ⅱ可能可以通过阻止 Src 蛋白激活影响其下游的 Ras／Raf／MEK／MAPK（ERK1／2或 p38）通路和 ERK1／2和p38细胞信号传导通路，下调 p38表达不仅直接和间接地诱导 T24细胞凋亡，而且可以阻止或减少 T24细胞的迁移、扩散和穿膜侵袭的发生。
목적：탐토 Src 락안산격매억제제Ⅱ대 Src 단백급기하유신호작용。방법채용반정량 RT-PCR 법검측 Src 락안산격매억제제Ⅱ처리후적인방광암세포 T24각농도조（0、0．2、1．0、5．0μmol／mL 조）적 c-Src、p38MAPK 기인표체적변화정황，사용 Western blot 검측 Src 락안산격매억제제Ⅱ처리후 T24세포내적 c-Src 단백린산화류형여비린산화류형적표체정황。결과Src 락안산격매억제제Ⅱ처리유하조후적인방광암세포 T24각농도조적 c-Src mRNA 적표체하조；p38기인적표체정축점하조추세。처리후 T24세포내 c-Src 기인재단백표체수평상기린산화류형수 Src 락안산격매억제제Ⅱ농도적증고표체축점하강，병차정제량효응관계。결론Src 락안산격매억제제Ⅱ가능통과경쟁 Src 단백린산화위점，사기불능격활，도치하유적세포전도도경실활사득 T24세포증식득도억제，인위 Src 단백구유작위방광이행세포암분자파향치료적잠재파점적가능성。Src 락안산격매억제제Ⅱ가능가이통과조지 Src 단백격활영향기하유적 Ras／Raf／MEK／MAPK（ERK1／2혹 p38）통로화 ERK1／2화p38세포신호전도통로，하조 p38표체불부직접화간접지유도 T24세포조망，이차가이조지혹감소 T24세포적천이、확산화천막침습적발생。
Objective To study the the molecular biology mechanism of Src Kinase InhibitorⅡon Cell Line T24.Methods Src expression and activation in T24 cell lines as well as Src Kinase InhibitorⅡ mediated inhibition of phosphorylation of Src were assayed with western blot.We examined the level of P38 in T24 cell lines as well as the effect of Src Kinase InhibitorⅡ on Src expression,activated by semi-quantitive RT-PCR.Results Phosphorylation Src protein expression was down regulation in T24 cell lines as well as Src Kinase InhibitorⅡ did its work.With Src Kinase InhibitorⅡ on T24 cells,expression of c-Src protein,p38 protein were down regulation.Conclusion Phosphorylation (activation),but not over-expression,of Src is crucial for the progression of BTCC.Phosphorylation Src protein play a pivotal role in regulating cell mi-gration and invasion in BTCC.2.Src Kinase InhibitorⅡ could reduce the proliferation of NSCLC cells by the inhibition of activated P38,three of the downstream signaling of Src.