反义硫代寡核苷酸与榄香烯乳剂合用抗乳腺癌活性的体外研究

In vitro Studies on the Synergistic Effect of Antisense Oligodeoxynucleotides and β-elemene on Proliferation of Breast Cancer Cell Lines

目的:研究以HER2mRNA为靶点的反义硫代脱氧寡核苷酸(S-ODNs)HA6722单用及与榄香烯乳剂合用时对HER-2过表达乳腺癌细胞株MDA-MB-453体外增殖的抑制作用。方法:选择HER2过表达的MDA-MB-453细胞与HER2低表达的MDA-MB-231细胞,MTT法观察HA6722单用及与榄香烯乳剂合用时对两种肿瘤细胞增殖的影响。结果:HA6722及榄香烯单用均可以剂量依赖方式抑制MDA-MB-453细胞的体外增殖,IC50值分别为41.8±8.1nmol·L-1和79.4±12.1nmol·L-1(n=3,mean±s)。加用低剂量的HA6722可增强榄香烯乳剂对MDA-MB-453细胞的抑制作用,IC50值由合用前的79.4±12.1nmol·L-1降至51.6±8.2nmol·L-1(n=3,P<0.05)。相反,在HER2低表达的MDA-MB-231细胞则没有这种增强作用;在IC50浓度下二者之间的联合指数(CI)为0.72±0.38(n=3)。结论:反义寡核苷酸HA6722与榄香烯乳剂合用对HER-2过表达乳腺癌细胞的体外增殖抑制具有协同作用。

Objective： To study the inhibitory effects of HER2 specific antisense oligodeoxynucleotide HA6722 administered alone or in combination with β-elemene on proliferation of breast cancer cell lines. Methods： MDA-MB453 and MDA-MB231 cell lines, which are HER2 over-and low-expressors, respectively, were used as experimental cells. Inhibitory effects of HA6722 alone or in combination with β-elemene on these cells were detected by means of methyl thiazolyl blue HA6722 and β-elemene could both inhibit the growth of MDA-MB453 cells in vitro in a dose-dependent manner with IC50 values of 41.8±8.1 nmol·L-1 and 79.4±12.1 nmol·L-1 （n=3）, respectively. When administered in combination with a low dose of HA6722, inhibitory effects of β-elemene on MDAMB453 cells increased markedly, resulting in significant decrease of IC50 from 79.4±12.1 nmol·L-1 to 51.6±8.2 nmol·L-1 （n= 3, P〈0.05）. The combination index （CI） was 0.72±0.38 （n=3）, which indicated a synergistic effect of these two drugs on HER2-overexpressing breast cancer cells. Conclusion： When administered in combination, antisense oligodeoxynucleotide HA6722 and β-elemene inhibit the growth of HER2-overexpressing breast cancer cells in a synergistic manner.