地塞米松诱导NK-92MI细胞株凋亡机制的研究

The mechanism for dexamethasone-induced apoptosis of NK-92MI cells

目的:探讨地塞米松(DEX)对NK-92MI细胞株杀伤活性及凋亡的影响及机制。方法:用不同浓度的DEX处理NK-92MI细胞:采用MTT比色法测定NK-92MI细胞的增殖率和对靶细胞的杀伤作用;流式细胞术检测NK-92MI细胞凋亡率;RT-PCR检测凋亡相关基因Bcl-2、Bax的表达。结果:浓度为1×10-8mol/L至1×10-3mol/L的DEX作用NK-92MI细胞24、48、72小时后,对其增殖均有明显抑制作用(P<0.05);效靶比为5∶1时,1×10-8mol/L至1×10-3mol/L的DEX对NK-92MI细胞杀伤活性均有抑制作用,与对照组相比有显著性差异(P<0.05);DEX可诱导NK-92MI细胞发生凋亡且凋亡诱导作用呈浓度时间依赖性;与对照组相比,DEX组Bcl-2基因表达降低(P<0.05),Bax基因表达增高(P<0.01)。结论:DEX可以抑制NK-92MI细胞增殖并且降低其杀伤活性,机制可能是通过诱导NK-92MI细胞凋亡,而后者与Bax/Bcl-2基因表达增高有关。

Objective：To study the effects of dexamethasone （DEX） on the cytotoxicity and apoptosis of NK-92MI cells and the mech- anisms involved. Methods： NK-92MI cells were treated with different doses of DEX. The proliferative rate and cytotoxicity of the NK-92MI cells were detected by MTT colorimetry. The cell apoptotic rate was observed by flow cytometry with Annexin V and propidium iodide（PI） double staining. The expression of apoptosis-related gene, Bcl-2 and Bax was detected by RT-PCR. Results： After treated with 1 × 10^-8mol/L to 1 ×10^-3moL/L of DEX for 24 h,48 h and 72 h, the proliferation of NK-92MI cells was significant inhibited（ P 〈 0.05）. The cytotoxicity of NK-92MI cells was inhibited by 1 × 10^-8mol/L to 1 × 10^-3mol/L of DEX at effector： target ratio of 5 ： 1 compared with that of the control group（ P 〈 0.05）. DEX induced apoptosis of NK-92MI cells in both time and dose depended manners. Results of RT-PCR showed that, compared with the control group, the expression of Bcl-2 decreased （ P 〈 0.05 ）, while Bax increased markedly in DEX group （ P 〈 0.01 ）. Conclusion：DEX can inhibit proliferation of NK-92MI cells and reduce its cytotoxicity, which may be caused by DEX-induced apoptosis of NK-92MI cells. file molecular mechanism of DEX-induced apoptosis of NK-92MI cells may be associated with the increasing expression of Bax/Bcl-2.