FK506 Attenuates the MRP1-Mediated Chemoresistant Phenotype in Glioblastoma Stem-Like Cells

Autor: María de Los Ángeles Toro, Ángelo Torres, Valentina Arriagada, C. Carrasco, Ignacio Niechi, Carlos Oyarzún, José Dellis Rocha, Claudia Quezada, José Ignacio Erices
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
multidrug resistance-associated protein 1
Apoptosis
Rats
Sprague-Dawley
lcsh:Chemistry
0302 clinical medicine
polycyclic compounds
Cytotoxic T cell
tacrolimus
lcsh:QH301-705.5
Spectroscopy
medicine.diagnostic_test
Glial fibrillary acidic protein
biology
Brain Neoplasms
Chemistry
General Medicine
Computer Science Applications
Phenotype
Vincristine
030220 oncology & carcinogenesis
Neoplastic Stem Cells
Multidrug Resistance-Associated Proteins
medicine.drug
endocrine system
Article
Catalysis
Flow cytometry
Inorganic Chemistry
03 medical and health sciences
In vivo
Cell Line
Tumor
medicine
ATP-binding cassette transporter
Animals
Humans
Viability assay
Physical and Theoretical Chemistry
Molecular Biology
neoplasms
Organic Chemistry
fungi
Nestin
Antineoplastic Agents
Phytogenic
nervous system diseases
030104 developmental biology
glioblastoma stem-like cells
lcsh:Biology (General)
lcsh:QD1-999
Drug Resistance
Neoplasm
Cancer research
biology.protein
Glioblastoma
multiple drug resistance
Zdroj: International Journal of Molecular Sciences, Vol 19, Iss 9, p 2697 (2018)
International Journal of Molecular Sciences
Volume 19
Issue 9
ISSN: 1422-0067
Popis: Poor response to current treatments for glioblastoma has been attributed to the presence of glioblastoma stem-like cells (GSCs). GSCs are able to expel antitumor drugs to the extracellular medium using the multidrug resistance-associated protein 1 (MRP1) transporter. Tacrolimus (FK506) has been identified as an MRP1 regulator in differentiated glioblastoma (GBM) cells (non-GSCs)
however, the effect of FK506 on GSCs is currently unknown. The objective of the following research is to evaluate the effect of FK506 on the MRP1-related chemo-resistant phenotype of GSCs. For this, U87MG and C6 glioma cell lines were used to generate non-GSCs and GSCs. mRNA and MRP1-positive cells were evaluated by RT-qPCR and flow cytometry, respectively. A Carboxyfluorescein Diacetate (CFDA)-retention assay was performed to evaluate the MRP1 activity. Apoptosis and MTT assays were employed to evaluate the cytotoxic effects of FK506 plus Vincristine (MRP1 substrate). GSC-derived subcutaneous tumors were generated to evaluate the in vivo effect of FK506/Vincristine treatment. No differences in transcript levels and positive cells for MRP1 were observed in FK506-treated cells. Lesser cell viability, increased apoptosis, and CFDA-retention in the FK506/Vincristine-treated cells were observed. In vivo, the FK506/Vincristine treatment decreased the tumor size as well as ki67, Glial Fibrillary Acidic Protein (GFAP), and nestin expression. We conclude that FK506 confers a chemo-sensitive phenotype to MRP1-drug substrate in GSCs.
Databáze: OpenAIRE
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