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作 者:何斌[1,2] 张育 周玮 高娜 高波 顾健 李建勇[1]
机构地区:[1]南京医科大学第一附属医院,江苏省人民医院血液科,江苏南京210029 [2]扬州大学临床医学院血液风湿科,江苏扬州225001
出 处:《中国实验血液学杂志》2009年第4期903-907,共5页Journal of Experimental Hematology
摘 要:为了探讨沙利度胺(thalidomide,THD)联合地塞米松(Dx)对多发性骨髓瘤KM3细胞的作用及其可能的机制,采用细胞毒性试验(MTT法)观察不同浓度、不同作用时间的THD或THD+地塞米松(Dx)作用于KM3细胞后细胞的抑制率,以选取最佳药物干预条件。使用该条件处理KM3细胞,并采用间接ELISA法检测细胞上清中IL-6、肿瘤坏死因子-α(TNF-α)、血管内皮细胞生长因子(VEGF)、内皮抑素(ES)、凋亡抑制蛋白survivin的表达。结果表明:随着THD浓度的加大、作用时间的延长,KM3细胞生长的抑制也呈增强的趋势,同时THD与Dx联用可显著提高药物对KM3细胞的生长抑制作用。80μg/ml或100μg/mlTHD联合Dx(4μg/ml)可使KM3细胞IL-6、TNF-α、survivin表达下降,ES表达增加,而对VEGF的表达无影响。结论:THD联合Dx对KM3细胞有协同抑制作用,THD联合Dx可能通过下调KM3细胞IL-6、TNF-α、survivin的表达,上调ES的表达而发挥抗多发性骨髓瘤的作用。The purpose of this study was to investigate the effect of thalidomide (THD) combined with dexamethasone (Dx) on multiple myeloma KM3 cells and its mechanism. The effect of the different concentrations and treatment time of THD or THD + Dx on KM3 cells was assayed by cytotoxicity test ( MTT mothod), the inhibitory ratio of THD or THD + Dx on the KM3 cell growth was detected for choosing the best intervention condition. The expression levels of IL-6, TNF-α, VEGF, ES, survivin in supernatant of cells treated with best intervention condition were measured by indirect ELISA. The results indicated that an enhancement of cell growth inhibition was observed in treated KM3 cells along with increasing of drug concentrations and prolonging of treatment times, at the same time the THD combined with Dx could significantly inhibit the KM3 cell growth. The combination of THD in concentration of 80 or 100 μg/ml with Dx in concentration of 4 μg/ml decreased the expression of IL-6, TNF-α and survivin, increased the expression of ES, while no influence on VEGF expression was found. It is concluded that THD combined with Dx shows the synergistic inhibitory effect on KM3 cells, they bring the effect resistant to multiple myeloma probably through down-regulating the expression of IL-6, TNF-α and survivin, and up-regulating the expression of ES in KM3 cell.
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