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

作　　者：孙君重[1] 夏绍友[2] 李留树[1] 宋海峰[3] 朱建华[1] 李秋文[1] 赵晖[1] 宋三泰[4] 

机构地区：[1]中国人民解放军总医院第304临床部,北京100039 [2]中国人民解放军总医院普外科,北京100039 [3]中国人民解放军总医院军事医学科学院放射医学研究所,北京100039 [4]中国人民解放军第307医院乳癌内科

出　　处：《肿瘤防治研究》2006年第3期137-140,共4页Cancer Research on Prevention and Treatment

基　　金：国家自然科学基金资助项目(30070895)

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。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 thiazolyi blue （MTT）, apoptosis was detected by means of TdT-Mediated dUTP nick end labeling （TUNEL）. Results HA6722 and paclitaxel could both inhibit the growth of MDA-MB-453 cell in vitro in a dose-dependent manner with the ICsovalue of 47. 6 ± 7.9nmol L^- 1 （n = 3, mean ± s） and 19. 4 ± 4. 1 nmol· L^- 1 （n = 3, mean ± s）, respectively. Low dose of HA6722 could enhance the inhibition effects of paclitaxel on MDA-MB-453 cells markedly, resulting in obveriously decrease of IC50 from 19. 4 ± 4. 1nmol· L^-1 to 13. 6 ± 5. 2nmol · L^-1 （n = 3, P〈0. 05） ; the combination index （CI） was 0. 81 0. 43（n = 3）, which indicated a synergetic effects of these two drugs on HER2 overexpressed breast cancer cells. When combine administered, the apoptosis of MDA-MB-453 cells was enhanced remarkable. Conclusion Antisense oligodeoxynucleotide HA6722 and paclitaxel could inhibit the growth of breast cancer cells, which is HER2 overexpression in a synergic mantlet.

关 键 词：反义 寡核苷酸 乳腺癌 HER2 mRNA 紫杉醇 

分 类 号：R73-362[医药卫生—肿瘤]