Department of Immunology, College of Basic Medical Science, China Medical University, Shenyang 110122, China.
Central Laboratory, Cancer Hospital of China Medical University, Shenyang 110042, China.
Int Immunopharmacol. 2018 Dec;65:312-322. doi: 10.1016/j.intimp.2018.10.023. Epub 2018 Oct 19.
This study was to explore the effect and mechanisms of anti- human gastric cancer by MENK in vitro and in vivo. The results showed in MENK-treated xenograft tissue, the percentage of M2-type macrophages decreased while M1-type macrophages increased. MENK increased the expression of M1-related cytokine TNF-α and attenuated the expression of M2-related cytokine IL-10 expression. MENK upregulated the expression of opioid receptor (OGFr), while it inhibited HGC27 and SGC7901 cells through blocking PI3K/AKT/mTOR signal pathway in vitro and in vivo. These effects of MENK could be cancelled when OGFr was knockdown. This indicates that binding to OGFr by MENK appears to be essential for the anti- GC cells. Therefore, it is concluded that MENK might skew macrophage toward M2 phenotype from M1 phenotype within tumor and induce cells apoptosis though blocking OGFr/PI3K/AKT/mTOR signaling pathway.
本研究旨在探讨 MENK 在体外和体内抗人胃癌的作用和机制。结果表明，在 MENK 处理的异种移植组织中，M2 型巨噬细胞的比例降低，而 M1 型巨噬细胞增加。MENK 增加了 M1 相关细胞因子 TNF-α 的表达，并减弱了 M2 相关细胞因子 IL-10 的表达。MENK 上调了阿片受体（OGFr）的表达，同时通过阻断 PI3K/AKT/mTOR 信号通路在体外和体内抑制 HGC27 和 SGC7901 细胞的生长。当 OGFr 被敲低时，MENK 的这些作用可以被取消。这表明 MENK 通过与 OGFr 结合，似乎对抗 GC 细胞是必不可少的。因此，研究认为 MENK 可能通过阻断 OGFr/PI3K/AKT/mTOR 信号通路，使肿瘤内的巨噬细胞从 M1 表型向 M2 表型倾斜，并诱导细胞凋亡。
