Geldanamycin inhibits proliferation and motility of human HER2/neu-overexpressing breast cancer cell line SKBr3 / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the antitumor effect of a benzoquinone ansamycin antibiotic, geldanamycin (GA), against HER2 /neu tyrosine kinase-overexpressing human breast cancer cell line SKBr3.</p><p><b>METHODS</b>To evaluate the antitumor activity of GA, the degradation of HER2 /neu tyrosine kinase in GA-treated SKBr3 cells was analyzed by Western blotting, their proliferation assessed using MTT assay, and the cell cycle distribution identified by flow cytometry. RT-PCR and Real-time PCR were employed to detect cyclin D1 mRNA expression and cell culture inserts model was used to evaluate the motility of the cells.</p><p><b>RESULTS</b>GA induced a dose- and time-dependent degradation of HER2 /neu tyrosine kinase and cell proliferation inhibition. GA treatment obviously decreased the survival rates of the cancer cells, leading also to a dose-dependent G(1) arrest. The antitumor effects of GA proved to be relevant with declined transcription of cyclin D1. The GA-treated cells also exhibited reduced motility.</p><p><b>CONCLUSION</b>GA can efficiently destabilize HER2 /neu tyrosine kinase and inhibit the proliferation and motility of human breast cancer cell line SKBr3 overexpressing HER2 /neu tyrosine kinase.</p>