The main problem precluding successful therapy with conventional taxanes is de novo or acquired resistance to taxanes. Therefore, novel experimental taxane derivatives (Stony Brook taxanes; SB-Ts) are synthesized and tested as potential drugs against resistant solid tumors. Recently, we reported alterations in ABCC3, CPS1, and TRIP6 gene expression in a breast cancer cell line resistant to paclitaxel. The present study aimed to investigate gene expression changes of these three candidate molecules in the highly resistant ovarian carcinoma cells in vitro and corresponding in vivo models treated with paclitaxel and new experimental Stony Brook taxanes of the third generation (SB-T-121605 and SB-T-121606). We also addressed their prognostic meaning in ovarian carcinoma patients treated with taxanes. We estimated and observed changes in mRNA and protein profiles of ABCC3, CPS1, and TRIP6 in resistant and sensitive ovarian cancer cells and after the treatment of resistant ovarian cancer models with paclitaxel and Stony Brook taxanes in vitro and in vivo. Combining Stony Brook taxanes with paclitaxel caused downregulation of CPS1 in the paclitaxel-resistant mouse xenograft tumor model in vivo. Moreover, CPS1 overexpression seems to play a role of a prognostic biomarker of epithelial ovarian carcinoma patients' poor survival. ABCC3 was overexpressed in EOC tumors, but after the treatment with taxanes, its up-regulation disappeared. Based on our results, we can suggest ABCC3 and CPS1 for further investigations as potential therapeutic targets in human cancers.

3rd Faculty of Medicine Charles University 100 00 Prague Czech Republic

Department of Gynecology and Obstetrics 3rd Faculty of Medicine and University Hospital Kralovske Vinohrady 100 00 Prague Czech Republic

Department of Pathology and Molecular Medicine 2nd Faculty of Medicine and Motol University Hospital 150 06 Prague Czech Republic

Division of Cell and Molecular Biology 3rd Faculty of Medicine Charles University 100 00 Prague Czech Republic

Institute of Chemical Biology and Drug Discovery Stony Brook University State University of New York Stony Brook NY 11794 USA

Laboratory of Pharmacogenomics Biomedical Center Faculty of Medicine Charles University 323 00 Pilsen Czech Republic

Toxicogenomics Unit National Institute of Public Health 100 00 Prague Czech Republic

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