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Mol Clin Oncol. 2018 Jun;8(6):719-724. doi: 10.3892/mco.2018.1608. Epub 2018 Apr 13.

Gene expression changes associated with chemotherapy resistance in Ewing sarcoma cells.

Author information

1
Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil.
2
Children's Cancer Institute (ICI), Porto Alegre, RS 90620-110, Brazil.
3
Pediatric Oncology Service, Clinical Hospital, Federal University of Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil.
4
Department of Pediatrics, Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS 90035-003, Brazil.
5
Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS 9005-170, Brazil.

Abstract

Ewing Sarcoma (ES) is a highly aggressive bone and soft tissue childhood cancer. The development of resistance to chemotherapy is common and remains the main cause of treatment failure. We herein evaluated the expression of genes associated with chemotherapy resistance in ES cell lines. A set of genes (CCAR1, TUBA1A, POLDIP2, SMARCA4 and SMARCB1) was data-mined for resistance against doxorubicin and vincristine, which are the standard drugs used in the treatment of patients with ES. The expression of each gene in SK-ES-1 ES cells was reported before and after exposure to a drug resistance-inducing protocol. There was a significant downregulation of CCAR1 and TUBA1A in doxorubicin-resistant cells, with low expression of TUBA1A in vincristine-resistant cells. By contrast, POLDIP2 was significantly upregulated in cells resistant to either drug, and the expression of the SMARCB1 and SMARCA4 genes was upregulated in doxorubicin-resistant cells. These findings indicate that resistance to specific chemotherapeutic agents was accompanied by differential changes in gene expression in ES tumors.

KEYWORDS:

chemoresistance; doxorubicin; drug resistance; pediatric cancer; vincristine

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