Azurocidin 1通过调节细胞噬菌体引发的细胞死亡来抑制三阴性乳腺癌的异常增殖。
Azurocidin 1 inhibits the aberrant proliferation of triple‑negative breast cancer through the regulation of pyroptosis.
发表日期:2023 Oct
作者:
Shanshan Lei, Shutong Li, Weiwei Xiao, Qiuping Jiang, Shifan Yan, Wen Xiao, Jiaodi Cai, Jingjing Wang, Lianhong Zou, Fang Chen, Yanjuan Liu, Yu Jiang
来源:
Cell Death & Disease
摘要:
Azurocidin 1(AZU1)是一种与肝素结合的蛋白质,在各种肿瘤中存在异常表达,但其在乳腺癌(BC)中的确切作用尚未明确。本研究旨在探讨AZU1与BC之间的关联。本研究应用生物信息学分析和Western blot分析检测BC组织中AZU1的表达水平。使用细胞计数试剂盒-8(Cell Counting Kit-8)试剂盒、克隆形成实验和流式细胞术分析AZU1对细胞增殖和细胞凋亡的影响。根据生物信息学分析,AZU1在组织中表达较低,并且与三阴性BC(TNBC)患者的生存率呈负相关。外源性AZU1刺激明显抑制TNBC细胞系的增殖和克隆形成。此外,流式细胞术的数据显示,外源性AZU1刺激促进了MDA-231和BT-549细胞的凋亡。由于火凤凰死亡是一种新型的细胞死亡方式,因此还研究了AZU1对火凤凰死亡特异标志物气孔蛋白D(GSDMD)表达的影响。本研究发现,在经过外源性AZU1处理后,TNBC细胞系中GSDMD及其上游调控因子[核因子κB(NF-κB)、NLR家族锥形域结构蛋白3(NLRP3)和半胱天冬酶-1(caspase-1)]显著增加,表明AZU1通过NF-κB/NLRP3/caspase-1轴对TNBC细胞系的火凤凰死亡有负调控作用。总的来说,本研究首次揭示了AZU1诱导TNBC火凤凰死亡的机制,通过调控pNF-κB/NLRP3/caspase-1/GSDMD轴,为TNBC的治疗干预策略的开发提供了新的思路。乳腺癌是女性最常见的癌症,仅次于肺癌在癌症相关死亡中位居第二位。
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.