酪氨酸激酶抑制剂抑制骨髓瘤细胞的增殖及黏附  

Tyrosine-kinase inhibitor inhibits proliferation and adhesion of multiple myeloma cell line RPMI8226 cells

作　　者：潘耀柱[1] 白海[1] 王存邦[1] 

机构地区：[1]兰州军区兰州总医院血液科,甘肃兰州730050

出　　处：《中国现代医学杂志》2008年第13期1863-1866,共4页China Journal of Modern Medicine

摘　　要：目的观察酪氨酸激酶抑制剂STI571对骨髓瘤细胞系RPMI8226细胞增殖、黏附以及黏附诱导耐药的影响。方法该试验采用MTT法检测STI571对骨髓瘤细胞增殖的影响;流式细胞仪检测对细胞周期的影响;结晶紫染色法分析RPMI8226细胞与纤连蛋白(fibronectin,FN)的黏附率;MTT法检测STI571对瘤细胞耐药的影响;结果STI571明显抑制RPMI8226细胞的增殖,24、48和72hIC50值分别为(34.52±2.31)、(28.46±1.58)和(25.74±2.44)μmol/L。25μmol/LSTI571处理24h,G1期细胞由55.8%增加至72.4%,S期细胞由34.8%减至15.6%。RPMI8226细胞与FN黏附1、6和12h,其黏附率分别为(43.71%±2.18%)、(55.63%±1.56%)和(63.42%±2.46%);非抑制浓度STI571(20μmol/L)处理1、6和12h后黏附率分别降为(15.12±1.04)%、(17.58±1.32)%和(17.24±1.59)%;组间差异有显著性(P<0.05);阿霉毒作用后,FN黏附组细胞IC50值[(1.46±0.04)μmol/L]显著高于BSA组[(0.78±0.03)μmol/L](P<0.05);FN联合STI571组IC50值[(0.81±0.05)μmol/L]与BSA联合STI571组[(0.74±0.02)μmol/L]相比差异无显著性(P>0.05),但却低于FN组(P<0.05)。结论STI571能抑制RPMI8226细胞的增殖、并可降低RPMI8226细胞与FN的黏附率及逆转黏附介导的阿霉素耐药。[Objective] To investigate the effects of tyrosine-kinase inhibitor STI571 on RPMI8226 cell proliferation, and adhesion of RPMI8226 cells to fibronectin, cell adhesion mediated adriamycin resistance. [Methods] By means of MTr assays, the proliferation of RPMI8226 cells was determined. Flow cytometry was used to observe cell cycle. By means of crystal violet staining and MTr assays, the adhesion of RPMI8226 cells to fibronectin and drug resistance mediated by cell adhesion were determined. [Results] The proliferation of RPMI8226 ceils was significandy inhibited by STI571, the ceil mean IC50 values were （34.52±2.31） μmol/L, （28.46±1.58）μmol/L,and （25.74± 2.44）μmol/L respectively after being cultured with STI571 for 24, 48, 72 hours. After being administrated 25μmol/L STI571 for 24 hours, RPMI8226 cells in G1 phase increased from 55.8% to 72.4%, and the one in S phase decreased from 34.8% to 15.6%. The results also showed that STI571 could inhibit the adhesion of RPMI8226 cells to fibronectin. When RPMI8226 ceils were adhered to FN or BSA-coated wells for 1, 6 and 12 hours the adhesion rates were （43.71±2.18）%, （55.63±1.56）%, and （63.42±2.46） %, accordingly. After the administration of Subtoxic concentrations of STI571 20μmol/L, the adhesion rates decreased to （15.12%±1.04%）, （17.58%±1.32%）, and （17.24%±1.59%）, respectively （P 〈0.05）. It was found that RPM18226 cells adhered to FN-coated plates had a significant survival advantage over those grown on BSA-coated plates when exposed to adriamycin （Adr） for 1 hour followed by a 24-hour culture period, and the mean IC50 value for FN-adhered cells obviously increased [（1.46±0.04） μmol/L] compared with BSA control [（0.78±0.03） μmol/L, P 〈0.05]. Following administration of 20 μmol/L ST1571,the mean IC50 values for FN and BSA adhered cells were （0.81±0.05） μmol/L, （0.74±0.02） μmol/L respectively, there was no significant difference between them （P 〉0.05）. [Conclusion] STI571 can inh

关 键 词：酪氨酸激酶抑制剂 ST1571 骨髓瘤细胞 增殖 黏附 

分 类 号：R733.71[医药卫生—肿瘤]