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

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.