The Role of TRIP6, ABCC3 and CPS1 Expression in Resistance of Ovarian Cancer to Taxanes

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 alt...

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Bibliographic Details
Published in:	International journal of molecular sciences Vol. 23; no. 1; p. 73
Main Authors:	Seborova, Karolina, Kloudova-Spalenkova, Alzbeta, Koucka, Kamila, Holy, Petr, Ehrlichova, Marie, Wang, Changwei, Ojima, Iwao, Voleska, Iveta, Daniel, Petr, Balusikova, Kamila, Jelinek, Michael, Kovar, Jan, Rob, Lukas, Hruda, Martin, Mrhalova, Marcela, Soucek, Pavel, Vaclavikova, Radka
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 22-12-2021 MDPI
Subjects:	Adaptor Proteins, Signal Transducing - genetics Animals Apoptosis Biomarkers Biomarkers, Tumor - genetics Breast cancer Cancer therapies Carbamoyl-Phosphate Synthase (Ammonia) - genetics Carcinoma, Ovarian Epithelial - drug therapy Carcinoma, Ovarian Epithelial - genetics Cell Line, Tumor Cell Survival - drug effects Cell Survival - genetics Chemotherapy Clinical trials CPS1 Down-Regulation - drug effects Down-Regulation - genetics Drug development Drug Resistance, Neoplasm - genetics Female Gene expression Genes Humans LIM Domain Proteins - genetics Medical prognosis Mice Mice, Nude Middle Aged multidrug resistance Multidrug Resistance-Associated Proteins - genetics Ovarian cancer Ovarian carcinoma Ovarian Neoplasms - drug therapy Ovarian Neoplasms - genetics Paclitaxel Paclitaxel - therapeutic use Patients Protein expression Proteins Signal transduction Solid tumors Stony Brook taxanes Taxanes Taxoids - therapeutic use Therapeutic targets Transcription Factors - genetics TRIP6 Tumors Xenografts Xenotransplantation ABCC3 multidrug resistance CPS1 TRIP6 taxanes ovarian carcinoma Stony Brook taxanes
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Summary:	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 , , and 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1422-0067 1661-6596 1422-0067
DOI:	10.3390/ijms23010073