Autor(es): Júnior, Luiz Antonio Lupi ; Cucielo, Maira Smaniotto ; Domeniconi, Raquel Fantin ; Dos Santos, Lucilene Delazari [UNESP] ; Silveira, Henrique Spaulonci ; Da Silva Nunes, Iseu ; Martinez, Marcelo ; Martinez, Francisco Eduardo ; Fávaro, Wagner José ; Chuffa, Luiz Gustavo De Almeida
Data: 2020
Identificador Persistente: http://hdl.handle.net/11449/199836
Origem: Oasisbr
Made available in DSpace on 2020-12-12T01:50:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-12-24
To investigate the potential role of immunotherapies in the cellular and molecular mechanisms associated with ovarian cancer (OC), we applied a comparative proteomic toll using protein identification combined with mass spectrometry. Herein, the effects of the protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride, known as P-MAPA, and the human recombinant interleukin-12 (hrIL-12) were tested alone or in combination in human SKOV-3 cells. The doses and period were defined based on a previous study, which showed that 25 μg/mL P-MAPA and 1 ng/mL IL-12 are sufficient to reduce cell metabolism after 48 h. Indeed, among 2,881 proteins modulated by the treatments, 532 of them were strictly concordant and common. P-MAPA therapy upregulated proteins involved in tight junction, focal adhesion, ribosome constitution, GTP hydrolysis, semaphorin interactions, and expression of SLIT and ROBO, whereas it downregulated ERBB4 signaling, toll-like receptor signaling, regulation of NOTCH 4, and the ubiquitin proteasome pathway. In addition, IL-12 therapy led to upregulation of leukocyte migration, tight junction, and cell signaling, while cell communication, cell metabolism, and Wnt signaling were significantly downregulated in OC cells. A clear majority of proteins that were overexpressed by the combination of P-MAPA with IL-12 are involved in tight junction, focal adhesion, DNA methylation, metabolism of RNA, and ribosomal function; only a small number of downregulated proteins were involved in cell signaling, energy and mitochondrial processes, cell oxidation and senescence, and Wnt signaling. These findings suggest that P-MAPA and IL-12 efficiently regulated important proteins associated with OC progression; these altered proteins may represent potential targets for OC treatment in addition to its immunoadjuvant effects.
Department of Anatomy Institute of Biosciences
Center for the Study of Venoms and Venomous Animals (CEVAP) UNESP - Universidade Estadual Paulista
Farmabrasilis RandD Division
Department of Structural and Functional Biology UNICAMP - University of Campinas
Department of Morphology and Pathology Federal University of São Carlos
Center for the Study of Venoms and Venomous Animals (CEVAP) UNESP - Universidade Estadual Paulista
