目的：探讨计算机辅助药物设计合成研发的特异性多肽A28增强顺铂对结肠癌细胞的杀伤效应。方法：以结肠癌细胞HCT116和人脐静脉内皮细胞（human umbilical vein endothelial cells, HUVEC）为实验对象，设定A28浓度为20 μmol/L，顺铂的浓度为10、30及90 μmol/L。MTT法检测A28联合顺铂对HCT116细胞和HUVEC细胞生长的影响，流式细胞术检测A28联合顺铂对HCT116细胞凋亡的影响。结果：顺铂浓度依赖性地抑制HCT116细胞的增殖，A28显著增强顺铂对HCT116细胞增殖的抑制及致凋亡作用。A28联合10 μmol/L顺铂对HCT116细胞增殖的抑制率为(43.3±0.03)%，显著高于单用顺铂组的（15.6±0.10)% (P<0.01)；进一步提高联合用药的顺铂浓度（30、90 μmol/L）时，对HCT116细胞增殖抑制率与10 μmol/L顺铂时没有显著差别(P>0.05)。A28联合1.1、3.3、10、30或90 μmol/L顺铂时，HCT116细胞的凋亡率\[(6.0±0.07)%、(14.5±0.03)%、(34.7±0.07)%、(37.3±0.08)%、(40.6±0.02)%\]高于单用顺铂组\[(5.1±0.06)%、(8.3±0.02)%、(14.6±0.08)%、(19.8±0.07)%、(32.6±0.02)%\]（P<0.01）。10 μmol/L顺铂联合20 μmol/LA28可以有效杀伤HCT116细胞，且对HUVEC的毒性作用较小。结论：多肽A28可提高顺铂对结肠癌细胞株HCT116的杀伤效果，减轻对正常HUVEC的毒性作用。

Objective:To study the effect of polypeptide A28, which was designed by computer aided drug designing system, on the cytotoxic effect of cisplatin against colon cancer cells. Methods: Colon cancer cell line HCT116 and human umbilical vein endothelial cells (HUVEC) were used in the present study. The concentration of polypeptide A28 was 20 μmol /L and those of cisplatin were 10, 30 and 90 μmol/L. The effects of polypeptide A28 combined with cisplatin on the growth of HCT116 and HUVEC cells were measured by MTT; their effects on the apoptosis of HCT116 cells were examined by flow cytometry. Results：Cisplatin dosedependently inhibited proliferation of HCT116 cells; A28 further enhanced the inhibitory effect of cisplatin on HCT116 cells and increased apoptosis induction effect of cisplatin on HCT116 cells, with the growth inhibition rate of the combination group being (43.3±0.03)%, which was significantly higher than that of the cisplatin single group (15.6±0.10)% (P<0.01). In combination group, when cisplatin concentrations (30, 90 μmol/L) were increased, the inhibitory effects on HCT116 cells were not increased compared with the 10 μmol/L cisplatin combination group (P>0.05). A28 combined with cisplatin (1.1, 3.3, 10, 30, or 90 μmol/L) induced apoptosis of more HCT116 cells than cisplatin single group did (P<0.01). Csplatin at 10 μmol/L combined with A28 at 20 μmol/L effectively killed HCT116 cells, whereas with less toxic effect on HUVEC cells. Conclusion：Polypeptide A28 can enhance the cytotoxic effect of cisplatin on colon cancer cell line HCT116 and decrease its lethal effect on HUVEC.

国家自然科学基金资助项目（No. 30772752）