丹参酮类化合物对K562细胞的生长抑制作用及其构效关系探讨

本研究比较丹参酮类化合物体外对K562细胞的增殖抑制作用,并探讨其结构与细胞毒性之间的关联性。采用改良MTT法测定不同浓度的丹参酮类化合物经与细胞共培养一定时间（24、48和72小时）后对K562细胞的增殖抑制作用;在倒置显微镜下观察不同的丹参酮类化合物对K562细胞的形态学影响。结果表明：所检测的丹参酮类化合物均能有效抑制K562细胞增殖,其抑制作用呈明显的时间和剂量依赖性。二氢丹参酮Ⅰ、丹参酮Ⅰ、丹参酮ⅡA、隐丹参酮作用24小时的IC50值分别为0.91、4.04、5.95、13.85μg/ml,而作用48小时的IC50值分别为0.37、1.35、1.71、6.71μg/ml,作用72小时的IC50值分别为0.33、0.46、0.82、6.02μg/ml。结论：4种丹参酮类化合物均对K562细胞均具有明显的增殖抑制作用,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,其具体作用机理尚有待探讨。

Inhibitory Effect of Tanshinones on Proliferation of K562 Cell Line and Its Structure-Activity Relationship

The study was purposed to investigate the growth inhibitory effect of tanshinones on K562 cell line and the relationship between their structures and cytotoxicity. The modified MTT assay was adopted to measure the inhibitory effect of tanshinones at different concentrations and chemical structures on K562 cells ,and the changes of cell morphology were observed by inverted phase contrast microscopy. The results indicated that the tanshinones could inhibit the proliferation of K562 cells effectively,and their cytotoxicities on K562 cells showed concentration- and time-dependent manners. The IC50 of dihydrotanshinoneⅠ,tanshinone Ⅰ,tanshinone ⅡA and cryptotanshinone at 24 hours were 0.91,4.04,5.95,13.85 μg/ml at 48 hours were 0.37,1.35,1.71,6.71 μg/ml; at 72 hours were 0.33,0.46,0.82,6.02 μg/ml,respectively. It is concluded that all of the four tanshinones have proliferation inhibitory effect on K562 cell line,among them the dihydrotanshinoneⅠ is the most active one,followed by tanshinoneⅠ,tanshinone ⅡA and cryptotanshinone subsequently,indicating that the chemical structure of aromatic ring A of tanshinones can enhance their cytotoxicity and the structure of furan ring C may influence the cytotoxicity,but their mechanism is still remained to be further investigated.