丙戊酸钠联合三氧化二砷对HL-60细胞株体外探究.docVIP

丙戊酸钠联合三氧化二砷对HL-60细胞株体外探究 　【摘要】 目的：探讨丙戊酸钠（sodium valproate， SV）联合三氧化二砷(arsenous trioxide， As2O3)诱导HL-60细胞凋亡与bcl-2﹑bax mRNA之间可能的关系。方法：在对数生长期的HL-60细胞中分别加入不同浓度的SV和1.0 μmol/L As2O3，采用MTT比色法测定细胞生长抑制率，用Annexin V-FITC/PI双重标记经流式细胞仪检测细胞早期凋亡率，RT-PCR检测bcl-2，bax mRNA在细胞中的表达。结果：SV抑制HL-60细胞生长并促进其凋亡， SV联合1.0 μmol/L As2O3对HL-60细胞的生长抑制及促凋亡作用更明显。SV单独或联合1.0 μmol/L As2O3作用于HL-60细胞，bcl-2 mRNA表达下降，bax mRNA表达增高。结论：SV与As2O3有协同作用，抑制HL-60细胞生长并诱导其凋亡， bcl-2﹑bax mRNA的表达变化可能参与了SV对HL-60细胞的促凋亡作用。 【关键词】 丙戊酸钠；三氧化二砷；HL-60细胞；凋亡；Bcl-2；Bax [Abstract] Objective: To study the growth inhibition and apoptosis of HL-60 cells affected by the combination of sodium valproate (SV) and arsenous trioxide (As2O3), and to explore the relationship between the apoptosis of HL-60 cells induced by the combination of SV and As2O3 and the expression of bcl-2 and bax mRNA. Methods: Various concentrations of SV and 1.0 μmol/L As2O3 were added to exponential growth HL-60 cells . MTT assays were used to measure the growth inhibitory effect of combination of SV and As2O3. Flow cytometry was used to evaluate their apoptosis. RT-PCR was adopted to measure the expression of bcl-2 and bax mRNA. Results: SV was able to induce growth inhibition and apoptosis in HL-60 cells. SV could enhance the growth inhibition and apoptosis induced by 1.0 μmol/L As2O3 alone. The expression of bcl-2 mRNA in HL-60 cells cultured with SV or the combination of SV and As2O3 decreased obviously, but the expression of bax mRNA increased. Conclusion: Combination of SV and As2O3 can synergistically inactivate HL-60 cells, inhibit the cell proliferation and induce apoptosis. The induction of apoptosis induced by SV or the combination of SV and As2O3 may be mediated by down-express bcl-2 mRNA and by up-express bax mRNA. [Key words] Sodium valproate； Arsenous trioxide; HL-60 cells； Apoptosis； Bcl-2; Bax 白血病是由于造血系统中某一系列细胞的异常增生，并在骨髓、肝、脾、淋巴结等各脏器广泛浸润的造血系统恶性肿瘤。传统的化疗药物在杀伤白血病细胞的同时，对正常骨髓细胞也产生不同程度的破坏。新型的化疗药物组蛋白脱乙酰基(histone deace-tylase，HDAC)抑制剂在体外对多种肿瘤细胞系有抑制增殖、诱导凋亡