LDL-ACM复合物对胃癌细胞株(SGC-7901,NKM-45)的细胞毒作用

CYTOTOXIC EFFECT OF LDL-ACLACINOMYCIN COMPLEX ON GASTRIC CARCINOMA CELL LINES

以低密度脂蛋白（LDL）作为脂溶性抗癌瘤药物阿克拉霉素（ACM）的载体，用四甲基偶氮唑蓝比色分析（MTT）、3H－TdR掺入及细胞蛋白质合成法研究了LDL－ACM复合物和游离ACM对胃癌细胞株（SGC－7901，NKM－45）以及正常人胃成纤维细胞的细胞毒作用。结果显示，LDL－ACM复合物对癌瘤细胞的杀伤作用明显强于游离ACM，对SGC－7901的杀伤作用尤其显著；而该复合物和游离ACM对胃成纤维细胞的作用无明显差异；LDL－ACM复合物对癌瘤细胞DNA及蛋白质合成的抑制作用显著大于游离ACM。提示LDL受体介导的药物细胞毒作用强于单独使用游离ACM，用LDL作为药物载体进行癌瘤导向治疗具有广阔发展前景。

Significant fow density lipoprotein(LDL)uptake by tumour cells led to the use of LDL as a discriminatory vehicle for the delivery of cytotoxic drugs. This study was to compare the cytotoxic effects of LDL-Aclacinomycin (ACM) complex and free ACM on human gastric carcinoma cell lines (SGC-7901, NKM-45 ) and human normal gastric fibroblasts(control cell) LDL-ACM complex was obtained by incubating LDL with a large excess of ACM at 40℃ for 3h. The results indicated that: (1)the complex contained 222.7 drug molecules per LDL; (2) the electrophoretic triobility on PAGE of the complex was similar to that of native LDL, indicating that both particles had an identical size; (3)MTT assay showed that the complex had more cytotoxicity on SGC-7901 and NKM-45 than free ACM and this toxic effect was higher on SGC-7901; (4) the complex has more DNA replication inhibition effect on SGC-7901 NKM-45 and fibroblasts than free ACM,and the effect of the complex on SGC-7901 NKM-45 was greater than that of on fibroblasts; (5) the complex exerted a higher inhibitory effect of cell protein synthesis on SGC-7901 and NKM45 than free ACM It can be concluded that incorporating ACM into LDL does not affect the recogonition of the complex by LDLR,the cytotoxic effect of the complex mediated by LDL R is greater than free drug,and therefore LDL may be used as a vehicle for drug targeting therapy to carcinoma cell.