二氢丹参酮Ⅰ对白血病THP1细胞的增殖抑制作用及其机制探讨

摘要

Objective To investigate the inhibition effect of dihydrotanshinoneI (DTA I) on the proliferation of leukemia THP1 cells and explore its action mechanism.Methods The THP1 cells were treated with various concentrations of DTA I for 24 h,48 h and 72 h,respectively.After treatment,the proliferation of the THP1 cells was determined by CCK8 assays.Flow cytometry was per-formed to examine the cell cycle and apoptosis of THP1 cells treated with 5 μmol/L of DTA I labeled with Annexin PI for 24 h.Western blot was used to detect the expression of the NF-kappa B,MAPK and PI3K.Results DTA I showed inhibitory effect on the prolifera-tion of THP1 cells.The calculated IC50 of DTA I for THP1 cells was 6.2 μmol/L,4.3 μmol/L and 4.1 μmol/L at 24 h,48 h and 72 h, respectively.After treated with 5 μmol/L of DTA I for 24 h,the percentage of apoptosis cells in the DTA I group was significantly higher than that in the control group(P<0.01).Compared with the control group,the proportion of cells in G0/G1phase was increased(P<0.01) and those in S phase and G2/M phase were decreased (P < 0.05).DTA I significantly inhibited the expression of NF-κB and PI3K,but did not affect the expression of MAPK.Conclusion We have confirmed that DTA I could inhibit the proliferation of THP1 cells,block the cell cycle,induce its apoptosis in dose and time dependent manner.The anticancer mechanisms of DTA I may be related to down-regulation of the expression of NF-κB and PI3K.%目的 探讨二氢丹参酮I对白血病THP1细胞的增殖抑制作用,并探讨其作用机制.方法 将不同浓度的二氢丹参酮Ⅰ与THP1细胞共孵24、48及72 h,分别采用CCK8法、Annexin V/PI双染法检测其对THP1细胞的增殖抑制与促凋亡作用;采用Western blot法检测NF-κB、MAPK及PI3K细胞信号通路的蛋白表达.结果 二氢丹参酮I与THP1细胞共孵24、48及72 h,其IC50值分别为6.2、4.3及4.1 μmol/L.浓度为5 μmol/L的二氢丹参酮Ⅰ与THP1细胞共孵24 h后,G0/G1期细胞比率均显著增加(P<0.01).二氢丹参酮Ⅰ可使NF-κB、PI3K信号通路的蛋白表达下调,对MAPK信号通路的蛋白表达无显著影响.结论 二氢丹参酮Ⅰ对THP1细胞具有增殖抑制作用并呈浓度及时间依赖性,其通过阻滞THP1细胞周期而促凋亡;其发挥抗肿瘤作用的机制可能与抑制NF-κB、PI3K细胞信号通路的蛋白表达有关.