雷公藤甲素通过调节microRNA21的表达干预K562/A02细胞的化疗敏感性

目的: 研究雷公藤甲素对K562/A02细胞多药耐药性的逆转作用，并探讨其机制。方法: 四甲基偶氮唑盐比色（MTT）法检测雷公藤甲素细胞毒性;采用非毒性浓度雷公藤甲素作用于K562/A02细胞，AnnexinV/PI双标法检测细胞凋亡;荧光定量PCR检测microRNA21表达水平;蛋白印迹法检测Bcl-2蛋白表达水平。microRNA21反义寡核苷酸转染K562/A02细胞，观察细胞增长率，凋亡率和Bcl-2表达的变化。结果: 非毒性浓度（5 nmol/L）雷公藤甲素明显增强K562/A02细胞对多柔比星的敏感性，并能增强多柔比星诱导细胞凋亡的作用，使K562/A02细胞平均凋亡率由4.3%明显上升到18.5%（P< 0.05）;雷公藤甲素作用后，microRNA21和Bcl-2蛋白水平降低;microRNA21反义寡核苷酸转染K562/A02细胞后，降低了Bcl-2表达，提高多柔比星敏感性和多柔比星诱导的细胞凋亡。 结论: 雷公藤甲素增强K562/A02细胞对多柔比星的敏感性，并诱导其凋亡，可能与下调microRNA21水平有关。

Triptolide enhance the sensitivity of doxorubicin via regulating microRNA21 expression in K562/A02 cell line

Objective: To investigate the reversal effects of triptolide on drug resistance in doxorubicin-resistant cells.Methods: Cell viability was measured by MTT assays.The K562/A02 cells were treated by triptolid at non-toxicity concentration.The apoptosis of cells were detected by Annexin V/PI methods.The expression of microRNA21 was measured by fluorescence quantitative polymerase chain reaction.Bcl-2 protein level were measured by western blot.After transfected with microRNA21 antisense oligonucleotide,the sensitivity to doxorubicin,the apoptosis of cells and Bcl-2 protein level were detected in K562/A02 cells.Results: Triptolide at non-toxicity concentration significantly enhanced sensitivity of K562/A02 cells to doxorubicin and promoted doxorubicin-induced apoptosis.Levels of microRNA21and Bcl-2 was significantly decreased after triptolide treatment.Transfection with microRNA21,a significant up-regulation of sensitivity to doxorubicin and a significant down-regulation of Bcl-2 protein was noted in K562/A02 cells.Conclusion: Triptolide significantly sensitizes K562/A02 cell to doxorubicin by inducing apoptosis and these effects of triptolide may be due to its down-regulation of microRNA21.