Abstract：
NLRP1 is predominantly overexpressed in breast cancer tissue, and the evaluated activation of NLRP1 inflammasome is associated with tumor growth, angiogenesis, and metastasis. Therefore, targeting NLRP1 activation could be a crucial strategy in anticancer therapy. In this study, we investigated the hypothesis that NLRP1 pathway may contribute to the cytotoxic effects of celecoxib and nimesulide in MDA-MB-231 cells. First of all, IC50 values and inhibitory effects on the colony-forming ability of drugs were evaluated in cells. Then, the alterations in the expression levels of NLRP1 inflammasome components induced by drugs were investigated. Subsequently, the release of inflammatory cytokine IL-1β and the activity of caspase-1 in drug-treated cells were measured. According to our results, celecoxib and nimesulide selectively inhibited the viability of MDA-MB-231 cells. These drugs remarkably inhibited the colony-forming ability of cells. The expression levels of NLRP1 inflammasome components decreased in celecoxib-treated cells, accompanied by decreased caspase-1 activity and IL-1β release. In contrast, nimesulide treatment led to the upregulation of the related protein expressions with unchanged caspase-1 activity and increased IL-1β secretion. Our results indicated that the NLRP1 inflammasome pathway might contribute to the antiproliferative effects of celecoxib in MDA-MB-231 cells but is not a crucial mechanism for nimesulide.
摘要：
NLRP1主要在乳腺癌组织中过表达，评估的NLRP1炎症小体的激活与肿瘤生长有关，血管生成,和转移。因此,靶向NLRP1激活可能是抗癌治疗的关键策略.在这项研究中,我们研究了NLRP1通路可能有助于塞来昔布和尼美舒利对MDA-MB-231细胞的细胞毒性作用的假设。首先,在细胞中评估IC50值和对药物集落形成能力的抑制作用。然后，研究了药物诱导的NLRP1炎性体成分表达水平的改变。随后，测量药物处理细胞中炎性细胞因子IL-1β的释放和caspase-1的活性。根据我们的结果,塞来昔布和尼美舒利选择性抑制MDA-MB-231细胞的活力。这些药物显著抑制细胞的集落形成能力。NLRP1炎性体成分的表达水平在塞来昔布处理的细胞中降低，伴随着caspase-1活性降低和IL-1β释放。相比之下,尼美舒利治疗导致相关蛋白表达上调，caspase-1活性不变，IL-1β分泌增加。我们的结果表明，NLRP1炎性体途径可能有助于塞来昔布在MDA-MB-231细胞中的抗增殖作用，但不是尼美舒利的关键机制。
