Evaluation of dose response curves within the MTT analysis for one agent and combination treatments was made by logistic regression analysis. A trend of consistent G2 M charge contact us was evidenced in the HeyA8 cell line through 48 h after experience of the inhibitor. But, in the SKOV3ip1 cell range, this 3 fold increase in G2 M arrest was current through 48 h after experience of the Aurora kinase inhibitor. Endoreduplication, a phenotype of Aurora B inhibition, is defined as a trademark of aberrant cytokinesis, therefore, we did flow cytometry to look at cell ploidy. Twenty-four hours after treatment with the inhibitor, 71% of the HeyA8 cells showed aneuploidy or 4N. Since a significant consequence of G2 M arrest is apoptosis, we used flow cytometry to determine the fraction of cells treated with the Aurora kinase inhibitor as represented by the sub G1 cell population. Within 48 h after Aurora kinase inhibition, a 30 fold increase in apoptotic HeyA8 cells was seen in contrast to controls. In the SKOV3ip1 cell line, therapy with the chemical elicited a 3. 5 7 fold increase in apoptosis by 48 h after exposure in contrast to controls. Depending on Metastatic carcinoma the induction of G2 M arrest by MK 0457, we next asked whether docetaxel caused apoptosis could be further increased by this inhibitor. Incorporating MK 0457 with docetaxel in the SKOV3ip1 cell line resulted in an immediate and sustained 25 to 40 fold increase in apoptosis start 12 h after-treatment and sustained through 48 h compared with controls. In vivo results of Aurora kinase inhibition on ovarian carcinoma To determine the optimal dose and frequency of dosing to efficiently inhibit Aurora kinase in vivo, we initiated dose finding trials using phospho histone H3 position as a biological indicator of Aurora kinase activity. Four twice daily doses of MK 0457 or vehicle alone were used by i. G. Procedure to athymic female mice bearing HeyA8 i. G. tumors 19 days after cyst cell inoculation once the tumors were palpable. Animals were sacrificed 24, 48, and 72 h after the last dose, and tumors were collected. Examination of the tumors by immunohistochemistry revealed 40% Icotinib to 50% lower levels of phospho histone H3 in the 25 and 50 mg/kg groups, respectively, within 24 h following the last dose of chemical. Although some amount of paid down phosphohistone H3 levels was observed at 48 h after the last dose of MK 0457, one of the most consistently observed response was at 24 h post treatment, consequently, following in vivo therapy studies applied MK 0457 dosed at 50 mg/kg beginning 24 h before taxane based chemotherapy. In vivo experiments with diverse cell lines within an orthotopic murine type for metastatic ovarian cancer were used to characterize the antitumor effects of Aurora kinase inhibition. The four treatment groups consisted of vehicle alone, MK 0457 twice-daily for 2 days weekly, docetaxel i. G. after weekly, and MK 0457 twice daily for 2 days weekly starting 1 day before weekly docetaxel or cisplatin.