title: Combined paclitaxel, cisplatin and fluorouracil therapy enhances ionizing radiation effects, inhibits migration and induces G0/G1 cell cycle arrest and apoptosis in oral carcinoma cell lines.
abstract: Although taxels (in particular paclitaxel), cisplatin and fluorouracil (TPF) chemotherapy has been approved for use in the treatment of head and neck squamous cell carcinoma (HNSCC), little is known with regard to the cellular mechanisms of this novel drug association. In order to investigate the reaction of cells to this novel treatment, the present study aimed to examine the cytotoxic effect of TPF in HNSCC cell lines in combination with irradiation, to analyze its effect on cell cycle progression and cell death, and to evaluate its ability to alter cell migration. An MTT assay was used to determine cell viability following TPF and cisplatin treatments in two human HNSCC cell lines (FaDu and SCC-9) and one keratinocyte cell line (HaCaT). The concurrent use of TPF or cisplatin and irradiation was also analyzed. Flow cytometric analysis was utilized to determine the cell cycle distribution and to verify the induction of apoptosis. The capacity of the drugs to alter oral cancer cell migration was also evaluated using a Transwell migration assay. The results indicated that TPF and cisplatin were cytotoxic to all cell lines, and enhanced the effects of ionizing radiation. FaDu cells were significantly more sensitive to the two treatments, and TPF was more cytotoxic than cisplatin for all cells. Flow cytometric analysis revealed that TPF increased the number of cells in G0/G1 phase in the SCC-9 cell line, and indicated apoptotic cell death. The results of the Transwell assay demonstrated that TPF inhibited migration in oral carcinoma cell lines. The results of the present study indicated that TPF functions in oral carcinoma cell lines through the enhancement of ionizing radiation effects, inducing cell cycle arrest at G0/G1 and apoptosis, in addition to inhibiting migration.
authors.affiliation: Faculty of Health Sciences, Campus Darcy Ribeiro, University of Brasília, Brasília, Federal District 70910-900, Brazil.
authors.forename: Silvia Taveira
authors.initials: ST
authors.lastname: Elias
authors.affiliation: Faculty of Health Sciences, Campus Darcy Ribeiro, University of Brasília, Brasília, Federal District 70910-900, Brazil.
authors.forename: Gabriel Alvares
authors.initials: GA
authors.lastname: Borges
authors.affiliation: Faculty of Health Sciences, Campus Darcy Ribeiro, University of Brasília, Brasília, Federal District 70910-900, Brazil.
authors.forename: Daniela Fortunato
authors.initials: DF
authors.lastname: Rêgo
authors.affiliation: Center of High Complexity in Oncology, University Hospital of Brasília, Brasília, Federal District 70910-900, Brazil.
authors.forename: Luis Felipe Oliveira
authors.initials: LF
authors.lastname: E Silva
authors.affiliation: Center of High Complexity in Oncology, University Hospital of Brasília, Brasília, Federal District 70910-900, Brazil.
authors.forename: Samuel
authors.initials: S
authors.lastname: Avelino
authors.affiliation: Center of High Complexity in Oncology, University Hospital of Brasília, Brasília, Federal District 70910-900, Brazil.
authors.forename: João Nunes
authors.initials: JN
authors.lastname: DE Matos Neto
authors.affiliation: Faculty of Health Sciences, Campus Darcy Ribeiro, University of Brasília, Brasília, Federal District 70910-900, Brazil.
authors.forename: Luiz Alberto
authors.initials: LA
authors.lastname: Simeoni
authors.affiliation: Faculty of Health Sciences, Campus Darcy Ribeiro, University of Brasília, Brasília, Federal District 70910-900, Brazil.
authors.forename: Eliete Neves Silva
authors.initials: EN
authors.lastname: Guerra
keywords: apoptosis; cell cycle arrest; cell migration; cisplatin; fluorouracil; head and neck squamous cell carcinoma; irradiation; paclitaxel