丹参酮类化合物对SPC-A-1细胞的生长抑制及其构效关系探讨

Growth Inhibition of Tanshinones on SPC-A-1 Cell Line and their Structure-activity Relationship

背景与目的大量研究表明丹参酮类化合物具有体外抗肿瘤作用,但很少有人综合研究丹参酮类化合物对同一种肿瘤细胞的作用情况。本文旨在比较4种丹参酮类化合物对SPC-A-1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。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预定时间(24h、48h和72h)后对SPC-A-1细胞的增殖抑制作用;倒置显微镜下观察不同药物处理对于SPC-A-1细胞的形态学影响。结果丹参酮类化合物均能有效抑制SPC-A-1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24h的IC50值分别为2.77μg/mL、6.01μg/mL、>10μg/mL和>10μg/mL;作用48h的IC50值分别为1.80μg/mL、4.04μg/mL、8.12μg/mL、8.71μg/mL;作用72h的IC50值分别为1.36μg/mL、1.69μg/mL、3.81μg/mL、7.35μg/mL。结论 4种丹参酮类化合物均对SPC-A-1细胞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。

Background and objective Numerous studies have shown that Tanshinones have anti-tumor effects in vitro,but few studies were focusing on the anti-tumor activity of Tanshinones against one special cancer cell line.The aim of this study is to investigate the growth inhibition effect of four Tanshinones on SPC-A-1 cell line and the relationship between their structures and cytotoxicity.Methods The modified MTT assay was adopted to measure the inhibition effect of Tanshinones on SPC-A-1 cells at different concentrations at 24 h,48 h and 72 h,and the changes of cell morphology were observed by inverted phase contrast microscope.Results Tanshinones could inhibit the proliferation of SPC-A-1 cells effectively,and their cytotoxicities on SPC-A-1 cells are all in concentration-dependent and time-dependent manners.The IC50 of dihydroTanshinone I,Tanshinone I,Tanshinone IIA and Cryptotanshinone at 24 h were 2.77 μg/mL,6.01 μg/mL,over 10 μg/mL and over 10 μg/mL,at 48 h were 1.80 μg/mL,4.04 μg/mL,8.12 μg/mL,8.71 μg/mL,at 72 h were 1.36 μg/mL,1.69 μg/mL,3.81 μg/mL,7.35 μg/mL,respectively.Conclusion All of the four Tanshinones have proliferation inhibitory effects on SPC-A-1 cell line,among which the Dihydrotanshinone I is the most active one,followed by Tanshinone I,Tanshinone IIA and Cryptotanshinone subsequently.The results showed that the structure of aromatic ring A could enhance the cytotoxicity and the structure of furan ring C would influence the cytotoxicity,but the mechanism is still remained to be further investigated.