PPMP调控KBv_(200)细胞株mdr1基因表达逆转其多药耐药  

MODULATION OF MDR1 mRNA EXPRESSION AND REVERSION OF MULTI-DRUG RESISTANCE BY PPMP IN KBv_(200) CELL LINE

作　　者：袁匀[1] 王丽莉[1] 张积仁[1] 

机构地区：[1]第一军医大学珠江医院,广州510282

出　　处：《解放军医学杂志》2001年第3期163-165,共3页Medical Journal of Chinese People's Liberation Army

基　　金：国家自然科学基金资助课题! (编号 3 970 0 14 3 ;3 9870 813 )

摘　　要：为研究糖脂合成酶抑制剂苯基棕榈酰胺吗啡丙醇 (DL threo 1 phenyl 2 palmitoylamino 3 morpholi no 1 propanol·HCl,PPMP)对人恶性肿瘤多药耐药细胞株KBv2 0 0 多药耐药mdr1基因的mRNA表达的调控 ,以及PPMP对细胞株KBv2 0 0 的多药耐药性的逆转作用 ,作者应用体外细胞培养技术对细胞株KBv2 0 0 进行PPMP处理 ,用RT PCR技术分析PPMP处理前后细胞mdr1的mRNA表达 ,以流式细胞仪检测PPMP处理前后KBv2 0 0 及其敏感株KB细胞内罗丹明 12 3的药物浓度变化。结果显示 5 μmol/L、15 μmol/LPPMP可部分抑制KBv2 0 0 细胞mdr1mRNA表达 ,2 5 μmol/LPPMP可完全抑制KBv2 0 0 细胞mdr1mRNA表达 ;PPMP可增加KBv2 0 0 细胞内罗丹明荧光强度 ,随着PPMP浓度的增加 ,耐药细胞内的罗丹明荧光强度逐渐增大。提示PPMP对细胞株KBv2 0 0 的多药耐药基因mdr1有抑制作用 ,并可以逆转KBv2 0 0 的多药耐药性 。The current study was designed to investigate the effects of PPMP (DL-threo-1-phenyl-2- palmitoylamino-3-morpholino-1-propanol), a kind of glycolipids synthase inhibitor, on the modulation of mdr1 mRNA expression and the reversing effect of multi-drug resistance by PPMP in human malignancy KBv 200cell line. In vitro KBv 200 cells were treated with PPMP in different concentration, the alterations of mRNA expression of drug-resistant gene mdr1 in KB (sensitive cell line) and KBv 200 (before and after the treatment of PPMP) cells were analyzed by RT-PCR. Intracellular rhodamine(Rh123) concentration was measured by flow cytometry. PPMP was found to inhibit mdr1 gene expression of KBv 200 at the mRNA level, and complete inhibition appeared at 25μmol/L PPMP treatment for 48h. PPMP could increase intracellular Rh123 accumulation in resistant cell lines. This modulation of gene expression and Rh123 accumulation was directly correlated with the concentration of PPMP. It suggested that PPMP, a chemical inhibitor of glycolipids synthase, could modulate mdr1 expression at the mRNA level in a content dependent manner, PPMP possesses MDR-reversing activity.

关 键 词：多药抗药性 中性糖苷神经鞘脂类 MDR基因 肿瘤 多药耐药性 PPMP 

分 类 号：R73－34[医药卫生—肿瘤] R73－361[医药卫生—临床医学]