阿霉素前体药Ac-Phe-Lys-PABC-ADM通过ERK1/2途径促进胃癌细胞死亡

Cathepsin B Cleavable Novel Prodrug Ac-Phe-Lys-PABC-ADM Induces Cell Death Via ERK1/2 Pathway in MGC-803 Cells

目的:研究阿霉素前体药(PADM)对人胃癌细胞系MGC-803生长以及ERK1/2信号通路的影响。方法:培养MGC-803人胃癌细胞系,检测组织蛋白酶B的表达、PADM及阿霉素(ADM)对细胞生长的抑制作用、p-ERK1/2、ERK1/2和β-actin的表达,以及细胞周期。结果:MGC-803细胞系中组织蛋白酶B表达丰富;PADM和ADM对细胞生长呈剂量依赖性抑制作用;处理48 h时,PADM的半数抑制浓度(IC50)为14.9μmol/L,是ADM(IC50=4.9μmol/L)的3.04倍。与ADM相比,PADM显著下调p-ERK1/2水平,并使细胞周期停滞在G2/S期。结论:PADM可通过ERK1/2途径诱导细胞死亡。PADM与ADM抗肿瘤机制可能不同。

Objective： To study the effects of Ac-Phe-Lys-PABC-ADM（PADM） on MGC-803 cell line and ERK1/2 signaling pathway.Methods： MGC-803 cells were used in this study;cathepsin B expression, the cytotoxicities of PADM and ADM,p-ERK1/2,ERK1/2,and β-actin,and cell cycle were determined.Results： Abundant cathepsin B expression was observed in MGC-803 cell line,ADM and PADM triggered dose-dependent cytotoxicity and resulted in a significant reduction of cell viability;IC 50 of PADM was 14.9 μmol/L,which was 3.04-times higher than ADM（IC 50 = 4.9 μmol/L）.Compared with 4.9 μmol/L ADM,PADM（14.9 μmol/L） could significantly decrease p-ERK1/2,and retarded cell cycle at G 2/S phase.Conclusion： PADM induced cell death via ERK1/2 pathway.Anti-tumor mechanisms of PADM and ADM may be different.