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靶向HER-2 mRNA 反义硫代寡核苷酸体外抗乳腺癌活性研究[J]. 肿瘤防治研究, 2005, 32(12): 745-748. DOI: 10.3971/j.issn.1000-8578.831
引用本文: 靶向HER-2 mRNA 反义硫代寡核苷酸体外抗乳腺癌活性研究[J]. 肿瘤防治研究, 2005, 32(12): 745-748. DOI: 10.3971/j.issn.1000-8578.831
Inhibitory Effect of Antisense Ol igodeoxynucleotides Targeting HER-2 mRNA on Prol iferation of Breast Cancer Cell Line in Vitro[J]. Cancer Research on Prevention and Treatment, 2005, 32(12): 745-748. DOI: 10.3971/j.issn.1000-8578.831
Citation: Inhibitory Effect of Antisense Ol igodeoxynucleotides Targeting HER-2 mRNA on Prol iferation of Breast Cancer Cell Line in Vitro[J]. Cancer Research on Prevention and Treatment, 2005, 32(12): 745-748. DOI: 10.3971/j.issn.1000-8578.831

靶向HER-2 mRNA 反义硫代寡核苷酸体外抗乳腺癌活性研究

Inhibitory Effect of Antisense Ol igodeoxynucleotides Targeting HER-2 mRNA on Prol iferation of Breast Cancer Cell Line in Vitro

  • 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)HA6722对HER-2过表达乳腺癌细胞株MDA-MB-453体外增殖的抑制作用,及HA6722对肿瘤细胞HER-2表达的影响。方法 选择HER2过表达的MDA-MB-453细胞与HER2低表达的MDA-MB-231细胞,MTT法观察S-ODNs对肿瘤细胞增殖的影响,免疫细胞化学(ICC)与RT-PCR方法研究S-ODNs对细胞HER2蛋白及mRNA表达的影响。结果 HA6722可以剂量依赖方式抑制MDA-MB-453细胞的体外增殖,IC50值(41.8±8.1nmol·L-1,n=5,mean±s)显著低于对照序列Scramble6722(IC50=489.4±12.1nmol·L-1,n=5,P〈0.01)。HA6722在蛋白水平与mRNA水平显著抑制MDA-MB-453细胞中HER-2的表达;HA6722对MDA-MB-231细胞的体外增殖无显著影响(IC50=476.7±17.6nmol·L-1,n=5,P〉0.05)。结论 HA6722可序列特异性地抑制HER-2过表达乳腺癌细胞的体外增殖,其抑制增殖作用与靶细胞HER-2表达下调有关。

     

    Abstract: Objective  To study the inhibitory effects of HER2 specific antisense oligodeoxynucleotide HA6722 on the HER2 overexpression human breast cancer cell line, MDA-MB-453, and to ascertain the mechanism through which HA6722 works. Methods  MDA-MB-453 and MDA-MB-231 cell lines, which are HER2 over-and normal-espression, respectively, were set as our experimental cells. Inhibitory effects of HA6722 on these cells were detected by means of methyl thiazolyl blue (MTT), HER2 protein p185 and HER2 mRNA were detected by immunocytochemistry and RT2PCR. Results  Compared with its control sequence Scramble6722, HA6722 could inhibit the growth of MDA2MB2453 cell in vit ro in a dose-dependent manner, the IC50 value of HA6722 (41. 8 ±8. 1nmol·L -1 n = 5) was significantly lower than that of scramble6722 ( IC50 = 489. 4 ±12. 1 nmol·L -1, n = 5, P < 0. 01) . Furthermore, HA6722 could inhibit the expression of HER2 in MDA-MB-453 cells markedly at protein and mRNA level. On the other hand, HA6722 had no effect s on the proliferation of MDA2MB2231 cell ( IC50 = 476. 7 ±17. 6nmol·L -1,n = 5, P > 0. 05) . Conclusion  Antisense oligodeoxynucleotide HA6722 could inhibit the growth of breast cancer cell which is HER2 overexpression in sequence specific manner, and the inhibitory effects correlated with the down-regulation of HER2 in targeting cells.

     

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