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通过对熊果酸的3位和28位进行化学修饰,制备熊果酸衍生物UA-1。采用MTT法评价熊果酸及其衍生物UA-1对不同分化程度的人胃癌细胞株AGS、BGC、MKN45的生长抑制作用,发现UA-1对3种胃癌细胞均具有较强的生长抑制作用,尤其对MKN45细胞的生长抑制作用较UA提高了近3.5倍。通过琼脂糖凝胶电泳、Annexin-V/PI双染、PI单染和流式细胞术检测UA-1对MKN45细胞的凋亡诱导作用,发现UA-1能将MKN45细胞阻断在G0/G1期,并显著诱导细胞凋亡,其作用强度呈药物浓度依赖性。进一步采用WesternBlot法检测凋亡抑制蛋白Survivin的表达,发现UA-1诱导MKN45细胞凋亡的机制可能与下调Survivin的表达有关。
Ursolic acid derivative UA-1 was prepared by chemical modification of ursolic acid at positions 3 and 28. UA-1 was used to evaluate the growth inhibition effect of ursolic acid and its derivative UA-1 on human gastric cancer cell lines AGS, BGC and MKN45 with different differentiation degree by MTT method. It was found that UA-1 had a strong growth inhibitory effect on all three kinds of gastric cancer cells , Especially for the growth inhibition of MKN45 cells compared with UA increased by nearly 3.5 times. The apoptosis induced by UA-1 on MKN45 cells was detected by agarose gel electrophoresis, Annexin-V / PI double staining, PI single staining and flow cytometry. It was found that UA-1 blocked MKN45 cells in G0 / G1 Period, and significantly induced apoptosis, the intensity of its effect was drug concentration-dependent. Western Blot was further used to detect the expression of Survivin, and the mechanism of UA-1-induced apoptosis in MKN45 cells may be related to the downregulation of Survivin.