反义硫代寡核苷酸增强细胞毒药物抗乳腺癌活性的体外研究
A Study of Antisense Oligodeoxynucleotides As A Chemo-Sensitizer to Cytotoxic Agents on Proliferation of Breast Cancer Cell Lines in Vitro
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摘要: 目的研究以HER2mRNA为靶点的反义硫代脱氧寡核苷酸(SODNs)HA6722单用及与紫杉醇合用时对HER2过表达乳腺癌细胞株MDAMB453体外增殖的抑制作用。方法选择HER2过表达的MDAMB453细胞与HER2低表达的MDAMB231细胞,MTT法观察HA6722单用及与紫杉醇合用时对两种肿瘤细胞增殖的影响;以末端转移酶介导的dUTP切口末端标记法(TUNEL)检测细胞凋亡。结果HA6722及紫杉醇单用均可以剂量依赖方式抑制MDAMB453细胞的体外增殖,IC50值分别为47.6±7.9nmol·L1(n=3,mean±s)和19.4±4.1nmol·L-1(n=3,mean±s)。加用低剂量的HA6722可增强紫杉醇对MDAMB453细胞的抑制作用,IC50值由合用前的19.4±4.1nmol·L-1降至13.6±5.2nmol·L-1(n=3,P<0.05)。联合应用时,在IC50浓度下二者之间的联合指数(CI)为0.81±0.43(n=3),其对MDAMB453细胞的相互作用表现为正性协同作用。结论反义寡核苷酸HA6722与细胞毒药物紫杉醇合用对HER2过表达乳腺癌细胞的体外增殖抑制具有协同作用...Abstract: Objective To study the inhibitory effects of HER2 specific antisense oligodeoxynucleotide HA6722 administered along or in combination with paclitaxel on proliferation of breast cancer cell lines. Methods MDA-MB-453 and MDA-MB-231 cell lines, which are HER2 over- and normal-espression, respectively, were set as experimental cells. Inhibitory effects of HA6722 alone or in combination with paclitaxel on these cells were detected by means of methyl thiazolyl blue (MTT); apoptosis was detected by means of TdT-Me...
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