三氧化二砷对骨髓瘤细胞周期及其调节蛋白表达的影响

Effects of arsenic trioxide on cell cycle and expression of cyclin dependent kinase inhibitors of multiple mye-loma cells

目的 研究三氧化二砷 (As2 O3)对骨髓瘤细胞周期及其调节蛋白表达的影响 ,探讨As2 O3的药理机制。方法 利用流式细胞仪DNA含量分析法探讨As2 O3 对骨髓瘤细胞系HS Sultan周期的影响 ;用RT PCR方法进一步研究As2 O3 对细胞周期负性调控因子P15、P16和P2 1mRNA表达的影响。结果 As2 O3 使HS Sultan细胞主要阻滞于G0 G1 期 ,少部分阻滞于G2 M期 ,诱导S期细胞凋亡 ;未经As2 O3 处理的HS Sultan细胞P15和P16mRNA均无表达 ,在 1.0 μmol LAs2 O3 作用 2 4h后P15mRNA出现弱的阳性条带 ,48h和 72h后变为强阳性 ,P16mRNA则在 48h后见弱的阳性条带 ,72h后呈强阳性 ,P2 1mRNA在原有表达的基础上明显增强。结论 As2 O3 的药理作用之一是使细胞周期蛋白依赖性激酶抑制因子P15、P16和P2 1重新表达或表达增强 ,从而影响细胞增殖周期。

Objective To study the effects of arsenic trioxide(As 2O 3) on cell cycle and expression of cyclin dependent kinase inhibitors (CDKIs) in multiple myeloma (MM) cells, and explore its pharmacological mechanism. Methods The DNA content of MM cell line HS-Sultan was analyzed by flow cytometry after exposure to As 2O 3, the effects on expression of CDKI P15, P16 and P21 were studied by reverse transcriptase PCR. Results DNA flow cytometric analysis showed that As 2O 3 induced most of HS-Sultan cells, arrest at G 0/G 1 phase and a small fraction at G 2/M phase and apoptosis occurred mainly in S phase. There was no expression of P15 and P16 mRNA in untreated HS-Sultan cells and 1.0 μmol/L As 2O 3 could make them expressed after exposed 24 or 48 hours respectively. Expression of P21 mRNA was obviously elevated by As 2O 3 comparing with that of control. Conclusion One of the pharmacological mechanisms of As 2O 3 is to activate the expression of CDKI P15, P16 and P21, and consequently affect cell proliferation cycle.