多种化疗药对凋亡抑制蛋白Survivin在HL-60细胞中表达影响的研究(英文)

Expression of Survivin in HL-60 Cells Treated with Chemotherapeutic Drugs

目的通过研究HL-60细胞在多种化疗药物作用后mRNA和蛋白的改变,初步探讨Survivin基因和耐药性之间的关系。方法用合适浓度的柔红霉素(DNR)、米托蒽醌(MIT)和三氧化二砷(As2O3)作用于HL-60细胞,随后用RT-PCR检测给与药物作用的第1天和第3天HL-60细胞中Survivin mRNA的表达情况,用Western blot检测Survivin蛋白的表达情况。结果在给予化疗药的第1天,3组HL-60细胞中Survivin mRNA表达水平全部降低:其中DNR下降了10％,MIT下降40％(P< 0．01),As2O3下降了25％(P<0．01)。在第3天,给予DNR和MIT组的HL-60细胞中Survivin mRNA表达较第1天有明显的升高, 分别上升20％(P<0．05)和65％(P<0．01);但给予As2O3组的Survivin mRNA表达仍持续降低,仅为第1天的68％(P<0．01)。 Western blot检测发现给予DNR和MIT作用3天后的HL-60细胞中Survivin蛋白含量分别升高了14％和11％,而给予As2O3组则下降了82％。结论白血病细胞给予化疗药后Survivin表达降低然后升高的现象可能与化疗中耐药性的发生有关;而三氧化二砷因有着不同的作用机制,可能会在逆转耐药性上发挥重要的作用。

Objective： To explore the relationship between survivin and drug resistance, and the changes of the survivin expression in HL-60 cells treated with three kinds of chemotherapeutic drugs. Methods： HL- 60 cells were treated with appropriate concentration of daunomycin （DNR）, mitoxantrone （MIT） or arsenic trioxide （As2O3）. The expression of survivin mRNA and protein on the first or third day was detected by RT-PCR and Western blot respectively. Results： The expression of survivin mRNA was decreased on the first day by 10% in DNR-treated group, 40% in MIT-treated group （P〈0.01） and 25% in As2O3-treated group （P〈0.01） respectively. On the third day, the expression of survivin mRNA in DNR- and MIT-treated group was up-regulated to 120% （P〈0.05） and 165% （P〈0.01） respectively as compared with that on the first day, but down-regulated to 68% in As2O3-treated group （P〈0.01）. As compared with control group, the expression of survivin protein in DNR- or MIT-treated group was increased by 14% or 11% on the third day respectively, but it was decreased by 18% in As2O3-treated group. Conclusion： In DNR- and MIT-treated group, the expression of surivin was decreased at first and then increased obviously, which may be one of the causes for resistance to chemotherapy against leukemia. Different from other two drugs, As2O3 may play an important role in restoring chemotherapy sensitivity.