title: 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.
abstract: 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 α5, α6 and β3 integrin subunits in the establishment/development of epithelial ovarian cancer (EOC), such as proliferation, migration, invasion, and response to carboplatin. The translation of the α5, α6 and β3 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 α5, α6, and β3 integrins does not affect the survival of morphants. Wound healing and transwell chamber assays showed that blocking α5 and α6 integrins decrease, in lesser and greater level respectively, the migratory and the invasive capacity of SKOV-3 cells. Finally, blocking α5 and α6 integrins partially sensitized the cells response to carboplatin, while blocking integrin β3 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 α5 and α6 integrins could become good candidates for chemotherapy targets in EOC.
authors.affiliation: Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, Delegación Gustavo A. Madero, Ciudad de México 07360, Mexico. Electronic address: jcvillegas@cinvestav.mx.
authors.forename: Julio César
authors.initials: JC
authors.lastname: Villegas-Pineda
authors.affiliation: Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, Delegación Gustavo A. Madero, Ciudad de México 07360, Mexico. Electronic address: toledo_leyva@hotmail.com.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Toledo-Leyva
authors.affiliation: Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, Delegación Gustavo A. Madero, Ciudad de México 07360, Mexico. Electronic address: clostrujillo2@yahoo.com.mx.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Osorio-Trujillo
authors.affiliation: Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, Delegación Gustavo A. Madero, Ciudad de México 07360, Mexico. Electronic address: arturomvi@hotmail.com.
authors.forename: Verónica Ivonne
authors.initials: VI
authors.lastname: Hernández-Ramírez
authors.affiliation: Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, Delegación Gustavo A. Madero, Ciudad de México 07360, Mexico. Electronic address: ptr@cinvestav.mx.
authors.forename: Patricia
authors.initials: P
authors.lastname: Talamás-Rohana
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D016190:Carboplatin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D015194:Diffusion Chambers, Culture; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039482:Integrin alpha5 / Q000235:genetics* / Q000378:metabolism; D039503:Integrin alpha6 / Q000235:genetics* / Q000378:metabolism; D039661:Integrin beta3 / Q000235:genetics / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology*; D010053:Ovary / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014176:Protein Biosynthesis / Q000187:drug effects*; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D039482:Integrin alpha5; D039503:Integrin alpha6; D039661:Integrin beta3; D009025:Morpholines; D016190:Carboplatin
keywords: Carboplatin; Epithelial ovarian cancer; Fibronectin; Integrin; Invasion; Migration; Morpholine