序贯顺序对反义硫代寡核苷酸联合赫赛汀抗乳腺癌活性的影响  

Studies on Sequence-dependent Inhibition of Antisense Oligodeoxy-nucleotides in Combination with Monoclone Antibody Herceptin in Breast Cancer Cell Lines in vitro

作　　者：孙君重[1] 宋林萍[1] 蒋双[1] 宋海峰[2] 宋三泰[3] 江泽飞[3] 李留树[1] 

机构地区：[1]中国人民解放军总医院第304临床部,北京100039 [2]军事医学科学院放射医学研究所 [3]军事医学科学院附属307医院

出　　处：《中国药师》2006年第4期291-294,共4页China Pharmacist

基　　金：国家自然科学资助项目(30070895)

摘　　要：目的:研究以HER2 mRNA为靶点的反义硫代脱氧寡核苷酸(S-ODNs)}IA6722单用及以不同的顺序与赫赛汀合用时对HER2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乳腺癌细胞, MTT法观察HA6722单用及与赫赛汀合用时对该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:赫赛汀及HA6722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(62．71±18．39)nmol·L-1及(86．33±14．62)mol··L-1(n=3)。联合应用的顺序直接影响二者的交互作用,如先用HA6722再用赫赛汀,则在200 nmol·L-1的浓度下联合应用对MDA-MB-453细胞增殖抑制作用增强;反之则否。结论:反义寡核苷酸HA6722与单克隆抗体赫赛汀序贯应用顺序对其抗乳腺癌细胞增殖作用有重要影响。Objective： To study the inhibitory effects of HER2 specific antisense oligodeoxynucleotide HA6722 administered along or in combination with hereeptin （ a specific monoclone antibody against HER2 receptor） by different manner on proliferation of breast cancer celt lines. Method： MDA-MB-453, which is HER2 overexpression, was set as experimental cells. Inhibitory effects of HA6722 alone or in combination with herceptin on MDA-MB-453 cells were detected by means of methyl thiazolyl blue （MTF） ; apoptosis was detected by means of TdT-Mediated dUTP nick end labeling （TUNEL）. Result： herceptin and HA6722 could both inhibit the growth of MDA-MB-453 cell in vitro in a dose-dependent manner with the ICs0 value of （62.71 ± 18.39）nmol· L^-1 and （86.33 ± 14.62）nmol· L^-1（n = 3 ,mean ± s）, respectively; When HA6722 were administered prior to heceptin, enhanced inhibition were found at the concentration of 200 nmol· L^-1 in a sequence -dependent manner. Conclusion： When combine used, the combination order could affect the inhibition effects of antisense oligodeoxynucleotide HA6722 and herceptin on HER2 overexpressed breast cancer cells significantly.

关 键 词：反义 寡核苷酸 乳腺癌 

分 类 号：R735.2[医药卫生—肿瘤] R151.1[医药卫生—临床医学]