酪氨酸激酶抑制剂PD168393对HER2不同表达水平膀胱癌细胞株的作用研究  

Study on the results of different quantities of expression of HER2 of bladder carcinoma cell line after treated by the inhibitor of protein tyrosine kinase, PD168393

作　　者：邱学德[1] 刘乔保[2] 王田[2] 董虹[3] 杨慧[4] 

机构地区：[1]昆明医学院第二附属医院泌尿肾病中心,云南昆明650101 [2]云南省第一人民医院泌尿外科,云南昆明650031 [3]云南省第一人民医院基础医学研究室,云南昆明650031 [4]云南省第一人民医院病理科,云南昆明650031

出　　处：《中华肿瘤防治杂志》2006年第8期604-607,共4页Chinese Journal of Cancer Prevention and Treatment

摘　　要：目的:探讨酪氨酸激酶抑制剂PD168393对HER2不同表达水平的膀胱肿瘤细胞的作用。方法:用免疫组织化学法检测肿瘤细胞的HER2表达量,用不同浓度的PD168393作用于T24和BIU87细胞,MTT法检测细胞抑制率,流式细胞仪检测细胞的凋亡率。RT PCR检测SurvivinmRNA的表达。结果:T24细胞HER2表达阳性,BIU87细胞HER2表达阴性。PD168393作用T24和BIU87细胞72h的IC50浓度分别为316.8和2234.0pmol/L,两者差异有统计学意义,P=0.0025;而多柔比星对T24和BIU87细胞的IC50浓度分别为25.5和29.1mol/L,P=0.1000。用同一浓度的PD168393作用于T24和BIU87细胞72h后,诱导细胞的凋亡率分别为(76.2±5.5)%和(40.4±5.9)%,P=0.0100;而多柔比星诱导细胞的凋亡率分别为(64.1±6.4)%和(63.4±7.9)%,P=0.2500。与多柔比星比较,PD168393能明显降低肿瘤细胞Survivin mRNA的表达,尤其是T24细胞更为明显。结论:HER2表达水平不同的膀胱癌细胞对酪氨酸激酶抑制剂的敏感性不同,对HER2受体酪氨酸激酶信号传递途径的靶向治疗可能是一种新的治疗途径,值得进一步研究。OBJECTIVE：To study the results of different expression leves of HER2 of bladder carcinoma cell line which was treated by inhibitor of protein tyrosine kinase （PD168393）. METHODS： The expression of HER2 of bladder tumor cell line was detected with the immunocytochemical method. The rate of inhibition of cell was assayed by MTT. The rate of apoptosis of cells was assayed by the flow cytometer and the expression quantity of Survivin mRNA was assayed with RT-PCR, after the cell line was treated by PD168393 in different doses and time. RESULTS： T24 cell line showed HER2 positive and BIU87 showed negative. ICso of T24 and BIU87 revealed 316.8 pmol/L and 2 234.0 pmol/L （P=0. 002 5）, respectively, after treated by PD168393 for 72 hours, and when treated by adriamycin they showed 25.5 mol/L and 29.1 mol/L （P=0. 100 0）, respectively. The rates of cell apoptosis of T24 and BIU87 cell line revealed （76.2 ± 5.5） % and （40.4±5.9） %, P〈0. 010 0, respectively, when the cell line was treated by PD168393 with the same concentration. The rates of cell apoptosis, however, treated by adriamycin, showed （64.1 ± 6.4） % and （63.4±7.9）%, P=0. 250 0. PD168393 of decreased the quantity of expression of Survivin mRNA more than adriamycin, especially for T24 cell line. CONCLUSIONS： The different expression leves of HER2 have different sensitivities when treated by PD168393. Therefore, it might a new therapeutic method to aim at HER2 receptor-protein tyrosine kinase signal convection pathway. This therapeutic method is worthy of further study.

关 键 词：膀胱肿瘤/药理学 蛋白质酪氨酸激酶 /拮抗剂和抑制剂 原癌基因 细胞凋亡/药物作用 信号传导 

分 类 号：R737.14[医药卫生—肿瘤]