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 p
185 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.