DTIC ADA446698: Combined Inhibition of Chk1 and pdf

DTIC ADA446698: Combined Inhibition of Chk1 and

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In vitro colony formation studies demonstrated that UCN-01 and the MEK1/2 inhibitor PD184352 interacted to synergistically kill human mammary carcinoma cells (MDA-MB- 231, MCF7) . Athymic mice were implanted in the rear flank with either MDA-MB-231 or MCF7 cells and tumors permitted to form to a volume of 100 mm(exp 3) prior to a two day exposure of either Vehicle, PD184352 (25 mg/kg), UCN-01 (0.1-0.2 mg/kg) or the drug combination. Tumor volume was measured every other day and tumor growth determined over the following 30 days. Transient exposure of MDA-MB-231 tumors or MCF7 tumors to either PD184352 or UCN-01 did not alter tumor growth rate or the mean tumor volume in vivo 30 days after drug administration. In contrast, combined treatment with PD184352 and UCN-01 significantly reduced MDA-MB-231, and largely abolished MCF7 tumor growth. Tumor control values for both cell lines were 0.36. Collectively, these findings argue that UCN-01 and MEK1/2 inhibitors have the potential to suppress mammary tumor growth in vivo which is independent of estrogen dependency

• Creator/s: Defense Technical Information Center
• Date: 9/1/2005
• Year: 2005
• Book Topics/Themes: DTIC Archive, Dent, Paul, VIRGINIA COMMONWEALTH UNIV RICHMOND, *EXPOSURE(PHYSIOLOGY), *IN VIVO ANALYSIS, *COLONIES(BIOLOGY), *ESTROGENS, *BREAST CANCER, TRANSIENTS, VOLUME, MICE, THYMUS, GROWTH(PHYSIOLOGY), CELLS(BIOLOGY), DRUGS, NEOPLASMS, VALUE

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