ROSIGLITAZONE INHIBITS PROLIFERATION OF MDA-MB-231 BREAST CANCER CELLS

NUÑEZ M.; MARTÍN G; MEDINA V; MOHAMAD N; CRICCO G; MASSARI N; RIVERA E; BERGOC R

Mar del Plata, Buenos Aires, Argentina

Congreso; XLIII Annual Meeting of SAIB, Sociedad Argentina de Investigación en Bioquímica y Biología Molecular,; 2007

Rosiglitazone (Rosi) is an antidiabetic drug extensively used for insulin-resistant type 2 diabetes mellitus treatment, and also ehxibits antitumoral action in several malignant cell lines. We have previously demonstrated the antitumoral effect of Rosi on mammary tumors induced in rats. The aim of this work was to study the in vitro effect of Rosi alone or combined with tamoxifen (Tam) on MDA-MB-231 breast cancer cells. Cell growth was determined using the clonogenic assay and results indicated that Rosi inhibited proliferation in a dose dependent manner (IC50=30ìM). Rosi also produced a significant cell-cycle arrest in G0/G1 phase (69% vs. 50% in controls) analyzed by flow cytometry. In accordance, the doubling time increased after Rosi treatment (29.4 h vs. 24.9 h in controls), while the expression of the well known proliferation marker, PCNA, decreased significantly (63%). Rosi-induced inhibition of proliferation was associated with an increase in the number of senescent cells (3.7% vs 1.2% in controls) as assessed by â-Galactosidase staining. Although we observed an imbalance of the Bax/Bcl-2 ratio, no significative effect on induction of apoptosis was found. Similar effects were observed when Rosi was combined with 1ìM Tam. Further studies are needed to elucidate the potential therapeutic use of Rosi in hormone independent breast cancer.