Effect of Everolimus on Heterogenous Renal Cancer Cells Populations Including Renal Cancer Stem Cells.

Autor: Kornakiewicz A; Molecular Oncology Laboratory, Department of Oncology, Military Institute of Medicine, ul. Szaserów 128, 04-141, Warsaw, Poland. anna.kornakiewicz@gmail.com.; Postgraduate School of Molecular Medicine, Warsaw Medical University, Żwirki i Wigury 61, 02-091, Warsaw, Poland. anna.kornakiewicz@gmail.com., Czarnecka AM; Molecular Oncology Laboratory, Department of Oncology, Military Institute of Medicine, ul. Szaserów 128, 04-141, Warsaw, Poland., Khan MI; Molecular Oncology Laboratory, Department of Oncology, Military Institute of Medicine, ul. Szaserów 128, 04-141, Warsaw, Poland., Krasowski P; Molecular Oncology Laboratory, Department of Oncology, Military Institute of Medicine, ul. Szaserów 128, 04-141, Warsaw, Poland., Kotrys AV; Institute of Biochemistry and Biophysics Polish Academy of Sciences, Laboratory of RNA Biology and Functional Genomics, Pawińskiego 5A, 02-106, Warsaw, Poland., Szczylik C; Molecular Oncology Laboratory, Department of Oncology, Military Institute of Medicine, ul. Szaserów 128, 04-141, Warsaw, Poland.; Warsaw Medical University, Żwirki i Wigury 61, 02-091, Warsaw, Poland.
Jazyk: angličtina
Zdroj: Stem cell reviews and reports [Stem Cell Rev Rep] 2018 Jun; Vol. 14 (3), pp. 385-397.
DOI: 10.1007/s12015-018-9804-2
Abstrakt: The aim of this study was to compare effect of everolimus on growth of different renal cell carcinoma (RCC) populations and develop experimental design to measure the early response of everolimus in clear cell RCC (ccRCC) cell lines including renal cancer stem cells. Effect of everolimus on RCC cell lines which include primary (786-0) and metastatic (ACHN) RCC cell lines as well as heterogenous populations of tumor cells of different histological RCC subtypes (clear cell RCC and papillary RCC) was measured when treated with everolimus in the range of 1-9 µM. Gene expression profiling using microarray was performed to determine the early response to everolimus in ccRCC cell lines after optimizing concentration of drug. Gene Set Enrichment Analysis (GSEA) was done which mainly focused on basic genes related to mTOR, hormonal and metabolic pathways. Everolimus acts on RCC cells in a dose-dependent manner. In all examined cell lines IC50 dose was possible to calculate after the third day of treatment. In ccRCC lines (parental and stem cell) everolimus changes expression of mTOR complexes elements and elements of related pathways when treated with optimized doses of drug. Characteristic expression profile for ccRCC cells at an early exposure time to everolimus is to elucidate. Wevarie include some basic observations derived from data analysis in the context of mechanism of action of drug with a view to better understand biology of renal cancer cells.
Databáze: MEDLINE
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