{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T20:09:39Z","timestamp":1768075779840,"version":"3.49.0"},"reference-count":38,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2018,9,11]],"date-time":"2018-09-11T00:00:00Z","timestamp":1536624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1160777"],"award-info":[{"award-number":["1160777"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002850","name":"Fondo Nacional de Desarrollo Cient\u00edfico y Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["1121121"],"award-info":[{"award-number":["1121121"]}],"id":[{"id":"10.13039\/501100002850","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms19092697","type":"journal-article","created":{"date-parts":[[2018,9,11]],"date-time":"2018-09-11T11:40:02Z","timestamp":1536666002000},"page":"2697","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["FK506 Attenuates the MRP1-Mediated Chemoresistant Phenotype in Glioblastoma Stem-Like Cells"],"prefix":"10.3390","volume":"19","author":[{"given":"\u00c1ngelo","family":"Torres","sequence":"first","affiliation":[{"name":"Laboratorio de Patolog\u00eda Molecular, Instituto de Bioqu\u00edmica y Microbiolog\u00eda, Facultad de Ciencias, Universidad Austral de Chile, Valdivia 5090000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Arriagada","sequence":"additional","affiliation":[{"name":"Laboratorio de Patolog\u00eda Molecular, Instituto de Bioqu\u00edmica y Microbiolog\u00eda, Facultad de Ciencias, Universidad Austral de Chile, Valdivia 5090000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Ignacio","family":"Erices","sequence":"additional","affiliation":[{"name":"Laboratorio de Patolog\u00eda Molecular, Instituto de Bioqu\u00edmica y Microbiolog\u00eda, Facultad de Ciencias, Universidad Austral de Chile, Valdivia 5090000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda de los \u00c1ngeles","family":"Toro","sequence":"additional","affiliation":[{"name":"Laboratorio de Patolog\u00eda Molecular, Instituto de Bioqu\u00edmica y Microbiolog\u00eda, Facultad de Ciencias, Universidad Austral de Chile, Valdivia 5090000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Dellis","family":"Rocha","sequence":"additional","affiliation":[{"name":"Laboratorio de Patolog\u00eda Molecular, Instituto de Bioqu\u00edmica y Microbiolog\u00eda, Facultad de Ciencias, Universidad Austral de Chile, Valdivia 5090000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ignacio","family":"Niechi","sequence":"additional","affiliation":[{"name":"Laboratorio de Patolog\u00eda Molecular, Instituto de Bioqu\u00edmica y Microbiolog\u00eda, Facultad de Ciencias, Universidad Austral de Chile, Valdivia 5090000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristian","family":"Carrasco","sequence":"additional","affiliation":[{"name":"Departamento de Patolog\u00eda del Hospital Base de Valdivia (HBV), Valdivia 5090000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Oyarz\u00fan","sequence":"additional","affiliation":[{"name":"Laboratorio de Patolog\u00eda Molecular, Instituto de Bioqu\u00edmica y Microbiolog\u00eda, Facultad de Ciencias, Universidad Austral de Chile, Valdivia 5090000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Quezada","sequence":"additional","affiliation":[{"name":"Laboratorio de Patolog\u00eda Molecular, Instituto de Bioqu\u00edmica y Microbiolog\u00eda, Facultad de Ciencias, Universidad Austral de Chile, Valdivia 5090000, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev-pathol-011110-130324","article-title":"Glioblastoma: From molecular pathology to targeted treatment","volume":"9","author":"Cloughesy","year":"2014","journal-title":"Annu. 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