35008510 OR The Role of TRIP6, ABCC3 and CPS1 Expression in Resistance of Ovarian Cancer to Taxanes Dotaz Zobrazit nápovědu
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.
- MeSH
- adaptorové proteiny signální transdukční genetika MeSH
- chemorezistence genetika MeSH
- down regulace účinky léků genetika MeSH
- epiteliální ovariální karcinom farmakoterapie genetika MeSH
- karbamoylfosfátsynthasa (amoniak) genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- myši nahé MeSH
- myši MeSH
- nádorové biomarkery genetika MeSH
- nádorové buněčné linie MeSH
- nádory vaječníků farmakoterapie genetika MeSH
- paclitaxel terapeutické užití MeSH
- proteiny s doménou LIM genetika MeSH
- proteiny spojené s mnohočetnou rezistencí k lékům genetika MeSH
- taxoidy terapeutické užití MeSH
- transkripční faktory genetika MeSH
- viabilita buněk účinky léků genetika MeSH
- zvířata MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH