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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 investigate the effect of HER2 mRNA targeting antisense S-ODNs IA6722 alone or in combination with Herceptin on HER2-overexpressing breast cancer cell lines MDA-MB -453 in vitro.Methods: The breast cancer cell line MDA-MB-453 overexpressed by HER2 was selected. The effect of HA6722 alone or in combination with Herceptin on the proliferation of the tumor cells was observed by MTT assay. The dUTP nick end labeling (TUNEL) method was used to detect apoptosis. Results: Both Herceptin and HA6722 could inhibit the proliferation of MDA-MB-453 cells in vitro in a dose-dependent manner with IC50 values of (62.71 ± 18.39) nmol·L-1 and (86.33 ± 14) .62) mol · · L -1 (n = 3). The order of combination application directly affects the interaction between the two. For example, if Herceptin is reused with HA6722 first, the combination of 200 nmol·L-1 and 200 mgL·L-1 will enhance the proliferation of MDA-MB-453 cells; otherwise, . Conclusion: The antisense oligonucleotide HA6722 and monoclonal antibody Herceptin sequential application sequence has an important impact on the proliferation of breast cancer cells.