丹参酮ⅡA对HL-60细胞系体外诱导分化作用的研究

Tanshinone Ⅱ A induced differentiation of HL-60 cell line in vitro

从细胞形态和细胞增殖动力学进行研究发现，0.5μg／ml丹参酮ⅡA可诱导58％的HL-60细胞向中性粒细胞分化。其中，中晚幼粒46％，杆状及分叶核12％；细胞生长被明显抑制；Brdu标记李及PCNA阳性率分别为19．7％和30.3％均明显低于对照组，而与维甲酸组无差异；流式细胞仪检测发现，药物处理组细胞被阻止于G0／G1期，而S用细胞数明显减少，增殖指数降低，c-myc癌基因蛋白表达降低，c-fos癌基因蛋白表达明显增加。结果显示．丹参酮ⅡA可能通过影响它基因表达及DNA多策酶活性、抑制细胞DNA合成，从而抑制细胞增殖，诱导细胞分化。

OUr experiments proved that tanshinone Ⅱ A induced differentiation of HL-60 cells in terms of cell morphology,cell growth and proliferative kinetics and expression of oncogene. The results showed that 58% of HL-60 cells were induced into mature neu-trophils by 0. 5μg/ml tanshinone Ⅱ A in vitro for 4 day, in which metamyelocytes were 46%, banded and segmented neutr0Phils12%. Cell growth curve showed that cells growth were inhibited. Brdu incorporation assay and immuno-histochemical stain of PC-NA thowed that the Brdu labeling and PCNA Positive percentage were 19. 7% and 30. 3 %,respectively,lower than these of con-trols(25. 6% and 47. 0% ) .and no difference were found statistically comparied with those of ATRA group. Flow cytometry anal-ysis showed that tanshinone Ⅱ A caused cell cycle arrest in G0/G1 phase;inhibited cellular DNA synthesis;decreased expression ofc-myc gene and enhanced expression of c-fos gene. The effect of inducing differentiation of tanshinone I A on HL-60 cells mightbe associated with inhibitton of DNA synthesis,activity of DNA polymerase δand medulation of oncogene expression.