Kuroda Kengo, Fukuda Tomokazu, Krstic-Demonacos Marija, Demonacos Constantinos, Okumura Kazuhiko, Isogai Hiroshi, Hayashi Miwa, Saito Kazuki, Isogai Emiko
Laboratory of Animal Microbiology, Graduate School of Agricultural Science, Tohoku University, Sendai, 981-8555, Japan.
United Graduate School of Agricultural Sciences, Graduate School of Agricultural Science, Iwate University, Morioka, Iwate, Japan.
BMC Cancer. 2017 Jan 7;17(1):33. doi: 10.1186/s12885-016-3003-9.
Antimicrobial peptides (AMPs) play important roles in the innate immune system of all life forms and recently have been characterized as multifunctional peptides that have a variety of biological roles such as anticancer agents. However, detailed mechanism of antimicrobial peptides on cancer cells is still largely unknown.
miRNA array and real-time qPCR were performed to reveal the behavior of miRNA in colon cancer HCT116 cells during the growth suppression induced by the AMPs. Establishment of miR-663a over-expressing HCT116 cells was carried out for the evaluation of growth both in vitro and in vivo. To identify the molecular mechanisms, we used western blotting analysis.
miR-663a is upregulated by administration of the human cathelicidin AMP, LL-37, and its analogue peptide, FF/CAP18, in the colon cancer cell line HCT116. Over-expression of miR-663a caused anti-proliferative effects both in vitro and in vivo. We also provide evidence supporting the view that these effects are attributed to suppression of the expression of the chemokine receptor CXCR4, resulting in the abrogation of phosphorylation of Akt and cell cycle arrest in G2/M via p21 activation.
This study contributes to the understanding of the AMPs' mediated anti-cancer mechanisms in colon cancer cells and highlights the possibility of using AMPs and miRNAs towards developing future strategies for cancer therapy.
抗菌肽（AMPs）在所有生命形式的固有免疫系统中发挥着重要作用，最近被表征为具有多种生物学作用（如作为抗癌剂）的多功能肽。然而，抗菌肽对癌细胞作用的详细机制仍大多未知。
进行miRNA阵列和实时定量PCR，以揭示在抗菌肽诱导生长抑制过程中，miRNA在结肠癌HCT116细胞中的行为。构建miR-663a过表达的HCT116细胞，用于评估其体内外生长情况。为了确定分子机制，我们采用蛋白质印迹分析。
在结肠癌细胞系HCT116中，人组织蛋白酶抗菌肽LL-37及其类似肽FF/CAP18的施用上调了miR-663a。miR-663a的过表达在体外和体内均产生抗增殖作用。我们还提供了证据支持以下观点：这些作用归因于趋化因子受体CXCR4表达的抑制，导致Akt磷酸化的消除以及通过p21激活使细胞周期停滞在G2/M期。
本研究有助于理解抗菌肽在结肠癌细胞中介导的抗癌机制，并突出了使用抗菌肽和miRNA制定未来癌症治疗策略的可能性。
