4,′5,7三羟基异黄酮抗骨髓瘤细胞增殖机制的研究

Anti-myeloma Mechanism of the Study from Genistein

为了研究4′,5,7三羟基异黄酮(Genistein)能否抑制人多发骨髓瘤(multipule myeloma MM)细胞株XG1的增殖,研究Genistein处理骨髓瘤细胞后bcl-2、bcl-xl、CyclinD1、ICMA-1基因表达变化及骨髓瘤细胞中NF-kap-paB表达的变化,本文利用体外培养人多发骨髓瘤细胞株XG1,依据剂量梯度分别给予Genistein,用噻唑蓝染色法(MTT)观察不同药物浓度的Genistein对MM细胞的增殖影响;5、10、15μg/mLGenistein与溶剂对照组分别作用XG1细胞48 h后,半定量RT-PCR法检测XG1细胞bcl-2、bcl-xl、CyclinD1、ICMA-1基因表达;应用5μg/mLGenistein处理XG1细胞,用免疫组化法观察Genistein处理前后细胞内NF-kappaB的表达情况。结果发现,Genistein作用XG1细胞48 h,随浓度增加,细胞增殖逐渐下降;5、10、15μg/mL Genistein处理组mRNA的表达均低于溶剂对照组(P<0.05),伴随Genistein处理浓度逐渐增加,bcl-2、bcl-xl、CyclinD1、ICMA-1基因mRNA的表达逐渐下降;Genistein能够使NF-kappaB在XG1细胞内重新分布,胞浆内出现NF-kappaB表达,胞核内NF-kappaB表达下降。结果表明,Genistein可能通过下调骨髓瘤细胞核中NF-kappaB的表达来抑制bcl-2、bcl-xl、Cy-clinD1、ICMA-1基因mRNA的表达,进而抑制骨髓瘤细胞的增殖、粘附、转移。

To investigate the effect of genistein on proliferation and bcl-2, bcl-x1, CyclinD1, ICMA-1 gene expression and NF-kappaB distribution of myeloma XG1 cells, XG1 cells were studied objects and the cell growth was measured by MTT assay. Gene expression of bcl-2, bcl-xl, CyclinD1, ICMA-1 was measured by RT-PCR. Expression of NF-kappaB was detected by immunocytochemistry. After exposed to genistein 48 h, proliferation of XG1 was inhibited in concentration-dependent manner. Gene expression of bcl-2, bcl-x1, CyclinDl, ICMA-1 was decreased after incubation of XG1 cells with 5, 10,15 μg/mL genistein 48 h,Genistein decreased expression of NF-kappaB in XG1 cellular nucleus. Genistein can inhibited the proliferation, sticking, transfusion and gene expression of bcl-2, bcl-x1, CyclinD1, ICMA-1 of XG1 cells by decreasing expression of NF-kappaB in cellular nucleus.