Peptídeo sintético selecionado por phage display modula os transcritos de IL-1β e IL-6 em células de câncer de mama triplo negativo

Abstract

Breast cancer (BC) is the second most common malignant tumor in the world population, accounting for 2.3 million new cases in 2022 alone. Its diagnosis is limited to imaging tests and biopsy, and treatments face severe resistance. Thus, there is an urgent need for tools that enable more accurate detection and more effective treatment. In the previous study by our research group, four recombinant peptides were selected by Phage Display against a tumor antibody specific for BC. Currently, two of these chemically synthesized peptides were evaluated for their cytotoxicity in mammary tumor cells and quantification of the modulated cytokines after treatment. We hypothesize that the peptides are cytotoxic to cells and BC and that they modulate inflammation, one of the hallmarks of the disease. For this, MCF10-A mammary cells (non-tumorigenic) and MCF-7, MDA-MB453 and MDA-MB-231 tumor cells were cultured and cytotoxicity evaluated by the MTT method. The expression of genes encoding cytokines TGF-β, IL-6, IL-1β, IL-22 and IL-17 was quantified by RT-qPCR. No significant cytotoxicity was demonstrated by peptides B1 and B7 in the cell lines submitted to the trial. However, peptide B7 stood out for being more selective in the triple-negative cell line and less cytotoxic in the non-tumorigenic cell line at a concentration of 100 ng/mL over a 48-hour period. In the qPCR assay, B7 increased the expression of IL-1β and reduced that of IL-6 by MDA-MB231 cells. Therefore, the B7 peptide modulates the cytokine profile expressed by the CMTN cell line used in this study, so its effects on the tumor microenvironment still need to be elucidated.