反义硫代寡核苷酸与赫赛汀联合抗乳腺癌活性的体外研究  

Studies of Inhibitory Effects of Antisense Oligodeoxynucleotides in Combination with Herceptin in Breast Cancer Cell Lines In vitro

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

机构地区：[1]解放军总医院第304临床部,北京100037 [2]军事医学科学院放射医学研究所,北京100850 [3]军事医学科学院附属医院乳癌内科,北京100071

出　　处：《生物技术通讯》2006年第3期367-369,共3页Letters in Biotechnology

基　　金：国家自然科学基金项目(30070895)

摘　　要：目的:研究以人表皮生长因子受体2(HER2)mRNA为靶点的反义硫代脱氧寡核苷酸(S-ODNs)HA6722单用及与赫赛汀合用时对HER2过表达乳腺癌细胞株MDA-MB-453体外增殖的抑制作用,探索乳腺癌治疗的新方法。方法:选择HER2过表达的MDA-MB-453乳腺癌细胞,用噻唑蓝(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:HA6722及赫赛汀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(79.41±11.51)及(60.66±17.63)nmol/L(n=3,x±s)。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50及200nmol/L的浓度下联合应用对MDA-MB-453细胞的增殖抑制作用增强,但在800nmol/L的浓度下抗增殖作用并无进一步增强。结论:在适宜的浓度下,反义寡核苷酸HA6722与单克隆抗体赫赛汀序贯应用,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 herceptin（a specific monoclone antibody against HER2） on proliferation of breast cancer cell lines, and to search for new remedies for patients with breast cancer. Methods： 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（MTT）; apoptosis was detected by means of TdT-Mediated dUTP nick end labeling（TUNEL）. Results： HA6722 and herceptin could both inhibit the growth of MDA-MB-453 cell in vitro in a dose-dependent manner with the IC50 value of 79.41±11.51 and 60.66±17.63 nmol/L （n=3, x±s）, respectively. When HA6722 was administered prior to heceptin, enhanced inhibition was found at the concentration of 50 and 200 nmol/L（P〈0.05, n=3）, but no further enhancement was found beyond these concentrations. Conclusion： When used combined, antisense oligodeoxynucleotide HA6722 and heceptin could inhibit the growth of HER2 overexpressed breast cancer cells in a synergic manner at the appropriate concentration.

关 键 词：反义 寡核苷酸 乳腺癌 人表皮生长因子受体2mRNA 赫赛汀 

分 类 号：R73-362[医药卫生—肿瘤]