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目的比较丹参酮类化合物对人急性早幼粒细胞白血病NB4细胞的体外增殖抑制作用,并探讨其分子结构与细胞毒性之间的关系。方法采用改良MTT法测定不同浓度的丹参酮类化合物与细胞共培养一定时间后对NB4细胞的增殖抑制作用;采用倒置显微镜观察其细胞形态。结果供试丹参酮类化合物均能有效抑制NB4细胞的增殖,其抑制作用呈明显的时间和剂量依赖性。与NB4细胞共培养24 h后,二氢丹参酮Ⅰ与丹参酮Ⅰ的IC50值分别为1.86、3.62μg·mL-1,丹参酮ⅡA和隐丹参酮的IC50值均大于10μg·mL-1;共培养48 h后二氢丹参酮Ⅰ、丹参酮Ⅰ、丹参酮ⅡA、隐丹参酮的IC50值分别为0.65、1.41、1.83、5.41μg·mL-1;72 h后的IC50值分别为0.28、0.33、0.45、2.59μg·mL-1。结论 4种丹参酮类化合物对NB4细胞均具有增殖抑制作用,作用强度大小依次为二氢丹参酮Ⅰ、丹参酮Ⅰ、丹参酮ⅡA、隐丹参酮,提示丹参酮类化合物的A环为芳环时可增强细胞毒性,C环的呋喃环结构可能影响其细胞毒性。
Objective To compare the inhibitory effects of tanshinones on the proliferation of human acute promyelocytic leukemia NB4 cells in vitro and to explore the relationship between the molecular structure and cytotoxicity. Methods MTT assay was used to determine the inhibitory effect of different concentrations of tanshinones on the proliferation of NB4 cells co-cultured with the cells for a certain period of time. The morphology of the cells was observed by inverted microscope. Results The test tanshinone compounds can effectively inhibit the proliferation of NB4 cells, the inhibition was significantly time-and dose-dependent. The IC50 values of dihydrotanshinone I and tanshinone I were 1.86 and 3.62μg · mL-1, respectively, and the IC50 values of tanshinone ⅡA and cryptotanshinone were both higher than 10μg · mL-1 when cultured with NB4 cells for 24 h. IC50 values of post-dihydrotanshinoneⅠ, tanshinoneⅠ, tanshinoneⅡA, cryptotanshinone were0.65,1.41,1.83,5.41μg · mL-1, respectively.The IC50values after 72h were0.28,0.33,0.45,2.59μg · mL -1. CONCLUSION: The four kinds of tanshinones inhibit the proliferation of NB4 cells. The intensity of the three tanshinones is dihydrotanshinone Ⅰ, tanshinone Ⅰ, tanshinone Ⅱ A and cryptotanshinone. The results suggest that the tanshinones can increase cytotoxicity when the A ring is aromatic ring, The furan ring structure of the C ring may affect its cytotoxicity.