Gene expression profile of 5-fluorouracil metabolic enzymes in laryngeal cancer cell line: Predictive parameters for response to 5-fluorouracil-based chemotherapy

Autor(es)

Silva Galbiatti, Ana Livia ^[1] ; Caldas, Heloisa Cristina ^[2] ; Maniglia, Jose Victor ^[3] ; Pavarino, Erika Cristina ^[1] ; Goloni-Bertollo, Eny Maria ^[1]

Afiliação do(s) autor(es)

^[1] FAMERP, Sao Jose do Rio Preto Med Sch, Genet & Mol Biol Res Unit, UPGEM, BR-15090000 Sao Jose Do Rio Preto - Brazil

^[2] FAMERP, Lab Expt Immunol & Transplantat LITEX, BR-15090000 Sao Jose Do Rio Preto - Brazil

^[3] FAMERP, Otorhinolaryngol & Head & Neck Surg Dept, BR-15090000 Sao Jose Do Rio Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BIOMEDICINE & PHARMACOTHERAPY; v. 68, n. 5, p. 515-519, JUN 2014.
• Citações Web of Science: 3

Resumo

Background: 5-fluorouracil (5-FU) is an antifolate chemotherapeutic that has become established in many therapeutic regimes, but sensitivity variations and development of resistance are common problems that limit the efficiency of the treatments. Inter-individual variations to 5-FU outcome have been attributed to different expression profiles of genes related to folate metabolism. Methods: To elucidate the mechanisms of variations to 5-FU outcome, the authors investigated MTHFR, DHFR, TYMS and SLC19A1 folate genes expression for 5-FU response in laryngeal cancer cell line (Hep-2). Concentrations of 10, 50, and 100 ng/mL of 5-FU chemotherapeutic were added separately in Hep-2 cell line for 24 hours at 37 degrees C. Cell sensibility was evaluated with fluorescein isothiocyanate (FITC) label Bcl-2 by flow cytometry. The real-time quantitative PCR (qPCR) technique was performed for quantification of gene expression using TaqMan (R) Gene Expression Assay. ANOVA and Bonferroni's post hoc tests were utilized to statistical analysis. Results: The numbers of viable Hep-2 cells with 10, 50, and 100 ng/mL concentrations of 5-FU chemotherapy were 15.87, 28.3 and 68.9%, respectively. Statistical analysis showed significant association between control group and increased expression for TYMS gene in cells treated with 100 ng/mL/5-FU chemotherapy (P < 0.05). Conclusions: The authors found association between the highest 5-FU dose chemotherapy and increased expression levels for TYMS folate gene in laryngeal cancer cell line. Although these experiments were performed in vitro, the results suggest that genetic factors are thought to play an important role in drug metabolism and may be useful for predicting treatment outcomes. (C) 2014 Elsevier Masson SAS. All rights reserved. (AU)

• Processo FAPESP: 10/12930-4 - Avaliação de quimioterápicos, expressão gênica e quantificação de proteínas em carcinoma de cabeça e pescoço
• Beneficiário: Eny Maria Goloni Bertollo
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/12932-7 - Avaliação de quimioterápicos, expressão gênica e quantificação de proteínas em carcinoma de cabeça e pescoço
• Beneficiário: Ana Lívia Silva Galbiatti-Dias
• Modalidade de apoio: Bolsas no Brasil - Doutorado