热休克蛋白90抑制剂的活性初步评价

The Evaluation of Heat Shock Protein 90 Inhibitors

目的:初步评价经计算机模拟筛选的Fs系列化合物对A549细胞的增殖抑制作用与对热休克蛋白90活性的抑制。方法:首先采用SRB(磺基罗丹明B)法观察26个化合物对A549肿瘤细胞增殖抑制活性,再进一步应用Western Blot方法对此类化合物在蛋白水平上对热休克蛋白90活性的抑制进行评价。以热休克蛋白70的表达增加作为热休克蛋白90活性是否被抑制的参考指标。结果:在Fs系列化合物中Fs-1、Fs-8、Fs-24对A549细胞增殖有明显抑制,且能明显上调Hsp70蛋白的表达,但同时Hsp90蛋白的表达量并不受影响。其余化合物在两种方法中显示均无明显抑制作用。结论:在经计算机模拟筛选出的26种Fs系列化合物中Fs-1、Fs-8、Fs-24可抑制A549细胞的增殖,可能是通过对Hsp90活性的抑制而发挥作用,经筛选其余Fs系列化合物抑制A549细胞增殖与抑制Hsp90活性作用均不显著。Fs-1、Fs-8、Fs-24类化合物作用的初步探索将为研制Hsp90靶向抑制剂类药物开辟新途径。

Objective： To preliminarily evaluate the inhibitory activity of the 26 compounds from computer simulation to A549 cells proliferation and heat shock protein 90 activity. Methods： Firstly, Sulfurhodamine B assay was adopted to evaluate the anti-proliferation activity of the compounds to A549 cells; Secondly, western blot method was used to verify whether the activity of Hsp90 was influenced. We regard the increasing expression of heat shock protein 70 as the suppressed activity of heat shock protein 90.Results： Among the compounds, Fs-1, Fs-8, Fs-24 inhibited the cell proliferation of A549 cells obviously, and enhanced the expression of heat shock protein 70 without having any effect on the expression of heat shock protein 90. Other compounds from computer simulation did not display any obvious effects. Conclusion： Compounds Fs-1, Fs-8, Fs-24 from computer simulation can inhibit the proliferation of A549 cells, which may affect through the activity inhibition of Hsp90. The other compounds may have no effect on the inhibition of proliferation and the activity of Hsp90. Therefore, the functions exploration of the compounds Fs-1, Fs-8, Fs-24 will probably provide new sight into the new medicine targeting Hsp90.