Azurocidin 1 inhibits the aberrant proliferation of triple‑negative breast cancer through the regulation of pyroptosis

Abstract

Azurocidin 1 (AZU1) is a heparin-binding protein which has been reported to be aberrantly expressed in various tumors, but its definite role in breast cancer (BC) has not been clarified. The aim of the present study was to explore the associations between AZU1 and BC. In the present study, bioinformatics and western blot analyses were applied to detect the expression level of AZU1 in BC tissues. The effect of AZU1 on cell proliferation and apoptosis was analyzed using Cell Counting Kit-8 assay, colony formation assay and flow cytometry. Based on bioinformatics analysis, AZU1 exhibited low expression in tissues and was negatively associated with the survival rate of patients with triple-negative BC (TNBC). Exogenous AZU1 stimuli significantly inhibited the proliferation and colony formation of TNBC cell lines. Furthermore, the data of flow cytometry revealed that exogenous AZU1 stimuli enhanced apoptosis in MDA-231 and BT-549 cells. As pyroptosis is a new type of cell death, the effects AZU1 played on the expression of gasdermin D (GSDMD), a specific biomarker of pyroptosis, were also investigated. The findings of the present study revealed that GSDMD, as well as its upstream regulators [NF-κB, NLR family pyrin domain containing 3 (NLRP3) and caspase-1], were significantly increased in TNBC cell lines when treated with exogenous AZU1, indicating that AZU1 contributed to the inhibition of pyroptosis of TNBC cell lines through the NF-κB/NLRP3/caspase-1 axis. Collectively, it was revealed for the first time, that AZU1 exposure promoted pyroptosis through the modulation of the pNF-κB/NLRP3/caspase-1/GSDMD axis in TNBC in vitro . The findings of the present study unveiled a novel mechanism of AZU1-induced pyroptosis in TNBC, which may aid in developing new strategies for therapeutic interventions in TNBC. breast cancer is the most commone form of cancer in women and is second only to lung cancer in terms of cancer-related mortality.

Revolutionizing breast cancer treatment: Harnessing the related mechanisms and drugs for regulated cell death (Review)

“…Azurocidin-1, a protein originating from neutrophils and predominantly stored in azurophilic granules, exerts its effects on pyroptosis in TNBC cells through the regulation of the pNF-κB/NLRP3/caspase-1/GSDMD axis. The identification of Azurocidin-1 holds promise in the development of novel immunotherapeutic approaches for the treatment of TNBC (137). The treatment of breast cancer cells with docosahexaenoic acid has been found to increase the activation of caspase-1 and GSDMD, enhance the secretion of IL-1β, promote the translocaton of high-mobility group protein B1 (HMGB1) to the cytoplasm and to lead to the formation of membrane pores.…”