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脉冲磁场对白血病细胞HL60/ADR多药耐药的逆转效果及分子机制研究
Mechanism of pulsed magnetic field on reversal of multi-drug resistance of the leukemic cell HL60/ADR
【摘要】 目的:探讨脉冲磁场(pulsed magnetic fields,PMF)对白血病细胞HL60/ADR多药耐药的逆转效果及其可能的分子机制。方法:生长曲线法检测PMF的细胞毒性;MTT法测定HL60、HL60/ADR的IC50及经不同参数PMF作用后HL60/ADR的IC50,计算耐药倍数和逆转倍数;流式细胞术检测PMF作用前后HL60/ADR细胞内药物蓄积变化及多药耐药相关蛋白(Multidrug Resis-tance Related Protein1 MRP1)阳性表达率的变化;RT-PCR法检测MRP1基因表达的变化。结果:单独PMF对HL60/ADR细胞的生长没有明显抑制作用,不同参数(频率为150Hz和250Hz,场强均为40mT,照射时间30min和1h)的PMF均能有效逆转HL60/ADR的多药耐药,150Hz/1h作用最为明显,逆转倍数为5.891倍。PMF作用后Rh123在HL60/ADR细胞内的蓄积增加了近8.0%,而MRP1基因表达下调了68.3%,蛋白阳性表达率下调23.6%。结论:PMF能够通过下调MRP1基因和蛋白的表达,进而增加Rh123在细胞内的蓄积,功能性部分逆转白血病细胞的多药耐药。
【Abstract】 Objective:To explore effect of Retinoic Acid(RA) on proliferation of human osteosarcoma MG-63 cells and its mechanism of antitumor.Methods:The MG-63 cells treated by 1μmol/L RA were subjected to growth curve counts,flow cytometry,immuncocytochemical assay and light microscopy.We investigated the influence of RA on proliferation,cellcycle,expression of associated oncogene and tumor suppressor gene of MG-63cells.Then we analyzed the mechanism of RA in inducing differentiation primarily.Results:Seven days after treated by 1 μmol/LRA,the inhibition rate of proliferation of MG-63 cells amounted to 42.2 % and RA reduced the rate of progression from G1 to S phase.The cells tended to be flat and spread.Meanwhile,the expression level of oncogene was downregulated and the expression level of tumor suppressor gene was upregulated.Conclusion:1μmol/L RA could inhibit proliferation of MG-63cells,reverse the malignant phenotype characters,downregulate expression of oncogene c-Myc,c-fos and upregulate expression of Tumor Suppressor Gene Rb,p27,as a result,induce MG-63 cells into differentiation effectively.
【Key words】 Human Osteosarcoma Cell MG-63; RA; Proliferation; Oncogene; Tumor Suppressor Gene;
- 【文献出处】 现代生物医学进展 ,Progress in Modern Biomedicine , 编辑部邮箱 ,2009年01期
- 【分类号】R733.71
- 【被引频次】5
- 【下载频次】115