DAC can restore expression of NALP1 to suppress tumor growth in colon cancer.
DAC can restore expression of NALP1 to suppress tumor growth in colon cancer.
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DOI：
10.1038/cddis.2014.532
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发表时间：
2015-01-22
影响因子：
9
通讯作者：
Zuo Y
中科院分区：
文献类型：
--
作者：
Chen C;Wang B;Sun J;Na H;Chen Z;Zhu Z;Yan L;Ren S;Zuo Y
尽管最近在鉴定结直肠癌的遗传和分子改变方面取得了进展，但确切的分子发病机制仍不清楚。 NALP1（核苷酸结合寡聚化结构域样受体家族，含热蛋白结构域 1）是核苷酸结合寡聚化结构域样受体蛋白家族的成员，该蛋白是炎症小体中的关键组织蛋白。据报道，NALP1在细胞凋亡、焦亡、炎症反应和自身免疫性疾病中发挥核心作用。 DAC (5-aza-2-deoxycytidine) 是一种抗肿瘤药物，可用于治疗肺癌、骨髓增生异常性疾病、骨髓增生异常和急性髓系白血病。在本研究中，我们利用组织微阵列、蛋白质印迹和定量实时PCR检测了人类正常和癌性结肠组织中NALP1的表达，并测量了DAC治疗前后三种结肠癌细胞系和动物模型中NALP1的表达。此外，我们在动物模型中检查了 DAC 对结肠癌的治疗效果。我们的数据表明，相对于肿瘤旁组织，NALP1 在人结直肠肿瘤组织中表达较低，并且与患者的生存和肿瘤转移相关。在体外和体内用 DAC 处理后 NALP1 的表达均增加。此外，DAC 抑制了小鼠模型中结肠癌的生长并延长了寿命。因此，我们得出结论，NALP1在结肠癌中低表达，与患者的生存和肿瘤转移相关，DAC治疗可以恢复NALP1水平，从而抑制结肠癌的生长。
Despite recent progress in the identification of genetic and molecular alternations in colorectal carcinoma, the precise molecular pathogenesis remains unclear. NALP1 (nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 1) is a member of the nucleotide-binding oligomerization domain-like receptor family of proteins that are key organization proteins in the inflammasome. It is reported that NALP1 plays a central role in cell apoptosis, pyroptosis, inflammatory reactions and autoimmune diseases. DAC (5-aza-2-deoxycytidine) is an antitumor drug useful to lung cancer, myelodysplastic disorders, myelodysplasia and acute myeloid leukemia. In this study, we examined the expression of NALP1 in human normal and cancerous colon tissues using tissue microarray, western blot and quantitative real-time PCR and we measured the expression of NALP1 in three kinds of colon cancer cell lines and animal models before and after treatment with DAC. Furthermore, we examined the treatment effects of DAC on colon cancer in our animal model. Our data indicate that NALP1 is expressed low in human colorectal tumoral tissues relative to paratumoral tissues and was associated with the survival and tumor metastasis of patients. The expression of NALP1 increased after treatment with DAC both in vitro and in vivo. Furthermore, DAC suppressed the growth of colon cancer and increased lifespan in mouse model. Therefore, we conclude that NALP1 is expressed low in colon cancer and associated with the survival and tumor metastasis of patients, and treatment with DAC can restore NALP1 levels to suppress the growth of colon cancer.