4.6 Article

The translational blocking of α5 and α6 integrin subunits affects migration and invasion, and increases sensitivity to carboplatin of SKOV-3 ovarian cancer cell line

Journal

EXPERIMENTAL CELL RESEARCH
Volume 351, Issue 2, Pages 127-134

Publisher

ELSEVIER INC
DOI: 10.1016/j.yexcr.2017.01.010

Keywords

Carboplatin; Epithelial ovarian cancer; Fibronectin; Integrin; Invasion; Migration; Morpholine

Funding

  1. CONACyT Basic Science and Health Ministry [221136, 233739]
  2. CONACYT fellowship [347078]

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Epithelial ovarian cancer is the most lethal gynecologic malignancy. Integrins, overexpressed in cancer, are involved in various processes that favor the development of the disease. This study focused on determining the degree of involvement of alpha 5, alpha 6 and beta 3 integrin subunits in the establishment/development of epithelial ovarian cancer (EOC), such as proliferation, migration, invasion, and response to carboplatin. The translation of the alpha 5, alpha 6 and beta 3 integrins was blocked using morpholines, generating morphant cells for these proteins, which were corroborated by immunofluorescence assays. WST-1 proliferation assay showed that silencing of alpha 5, alpha 6, and beta 3 integrins does not affect the survival of morphants. Wound healing and transwell chamber assays showed that blocking alpha 5 and alpha 6 integrins decrease, in lesser and greater level respectively, the migratory and the invasive capacity of SKOV-3 cells. Finally, blocking alpha 5 and alpha 6 integrins partially sensitized the cells response to carboplatin, while blocking integrin beta 3 generated resistance to this drug. Statistical analyses were performed with the GraphPad Prism 5.0 software employing one way and two-way ANOVA tests; data are shown as average +/- SD. Results suggest that alpha 5 and alpha 6 integrins could become good candidates for chemotherapy targets in EOC.

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