Oxaliplatin and irinotecan induce heterogenous changes in the EMT markers of metastasizing colorectal carcinoma cells
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
29842879
DOI
10.1016/j.yexcr.2018.05.032
PII: S0014-4827(18)30303-3
Knihovny.cz E-zdroje
- Klíčová slova
- ABCATP binding cassette, CRCColorectal cancer, Drug resistance, EMTEpithelial-mesenchymal transition, Epithelial-mesenchymal transition, ITIrinotecan, Irinotecan, MRPMultidrug resistance-associated protein, Metastatic colon cancer, OPTOxaliplatin, Oxaliplatin, Primary cell lines,
- MeSH
- adenokarcinom farmakoterapie metabolismus sekundární MeSH
- antitumorózní látky farmakologie MeSH
- chemorezistence MeSH
- epitelo-mezenchymální tranzice účinky léků MeSH
- invazivní růst nádoru MeSH
- irinotekan farmakologie MeSH
- kolorektální nádory farmakoterapie metabolismus patologie MeSH
- lidé MeSH
- lymfatické metastázy MeSH
- nádorové biomarkery genetika metabolismus MeSH
- nádorové buněčné linie MeSH
- oxaliplatin farmakologie MeSH
- patologická angiogeneze MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antitumorózní látky MeSH
- irinotekan MeSH
- nádorové biomarkery MeSH
- oxaliplatin MeSH
In patients with advanced colorectal cancer (CRC), surgery is complemented with systemic therapy - chemotherapy and radiochemotherapy. Although the patients' overall survival has been significantly improved, tumor resistance is still a frequent cause of chemotherapy failure. Several factors contribute to chemoresistance of tumor cells including changes related with epithelial-mesenchymal transition (EMT). The present study was designed to verify the presence of EMT markers in paired CRC primary cell lines obtained from primary tumor sites and lymph node metastases of three patients and to investigate the effect of irinotecan and oxaliplatin treatment on these markers as well. The samples of the higher stage of CRC and positive for angioinvasion were selected and qPCR, western blot analysis, migration assay, cytotoxicity testing was performed. Results confirmed the increased expression of several markers characteristic of EMT and invasiveness in lymph node metastatic cells, with a significant variability between individual samples. Irinotecan and oxaliplatin decreased migration activity of the cells and to the varying degree affected the expression of EMT and invasiveness markers. In conclusion, in CRC EMT is present in metastatic cells over a phenotypic continuum whose expression is altered heterogeneously upon irinotecan and oxaliplatin treatment.
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