Niclosamide inhibits colon cancer progression through downregulation of the Notch pathway and upregulation of the tumor suppressor miR-200 family.
Niclosamide inhibits colon cancer progression through downregulation of the Notch pathway and upregulation of the tumor suppressor miR-200 family.
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氯硝柳胺通过下调 Notch 通路和上调肿瘤抑制因子 miR-200 家族来抑制结肠癌进展
DOI：
10.3892/ijmm.2016.2689
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发表时间：
2016-09
影响因子：
5.4
通讯作者：
Zuo Y
中科院分区：
文献类型：
--
作者：
Suliman MA;Zhang Z;Na H;Ribeiro AL;Zhang Y;Niang B;Hamid AS;Zhang H;Xu L;Zuo Y
结直肠癌（CRC）是全世界癌症相关死亡的最常见原因之一。因此，需要开发用于治疗CRC的新的治疗方法。越来越多的证据表明，氯硝柳胺，驱虫药，发挥抗肿瘤活性的几种类型的癌症，包括结肠癌。然而，负责这种药物作用的潜在分子机制仍然难以捉摸。已有研究表明，Notch信号通路的异常参与了结肠癌的发生。在此，我们研究了氯硝柳胺对结肠癌细胞生长、迁移和凋亡的影响，以及Notch信号通路的作用。通过MTT法、创伤愈合实验和Transwell迁移实验，观察到氯硝柳胺抑制结肠癌细胞的生长和迁移，流式细胞仪检测到氯硝柳胺诱导细胞凋亡。这与Notch 1、Notch 2、Notch 3和Hey 1的蛋白表达降低以及肿瘤抑制因子microRNA（miR或miRNA）-200家族成员（miR-200 a、miR-200 b、miR-200 c、miR-141和miR-429）的表达增加相关，这些家族成员通常在结肠癌中下调。总的来说，这些发现表明氯硝柳胺通过下调Notch信号传导和上调miR-200家族成员可能抑制结肠癌的进展。
Colorectal cancer (CRC) is among the most frequent causes of cancer-related deaths worldwide. Thus, there is a need for the development of new therapeutic approaches for the treatment of CRC. Accumulating evidence has revealed that niclosamide, an anthelminthic drug, exerts antitumor activity in several types of cancer, including colon cancer. However, the underlying molecular mechanisms responsible for the effects of this drug remain elusive. Previous studies have shown that the aberrant Notch signaling pathway contributes to the carcinogenesis of colon cancer. Herein, we examined the effects of niclosamide on the growth, migration and apoptosis of colon cancer cells, and the role of the Notch signaling pathway. By performing MTT, wound-healing and Transwell migration assays, we observed that niclosamide suppressed the growth and migration of colon cancer cells, and flow cytometry demonstrated that cell apoptosis was induced. This was associated with the decreased protein expression of Notch1, Notch2, Notch3 and Hey1, and the increased expression of the tumor suppressor microRNA (miR or miRNA)-200 family members (miR-200a, miR-200b, miR-200c, miR-141 and miR-429) that are typically downregulated in colon cancer. Collectively, these findings demonstrate that niclosamide potentially inhibits the progression of colon cancer by downregulating Notch signaling and by upregulating the miR-200 family members.