Combination of Inositol Hexaphosphate and Inositol Inhibits Liver Metastasis of Colorectal Cancer in Mice Through the Wnt/β-Catenin Pathway
Combination of Inositol Hexaphosphate and Inositol Inhibits Liver Metastasis of Colorectal Cancer in Mice Through the Wnt/β-Catenin Pathway
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DOI：
10.2147/ott.s247646
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发表时间：
2020-01-01
影响因子：
4
通讯作者：
Song, Yang
中科院分区：
文献类型：
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作者：
Liu, Xiaohan;Liu, Cuiping;Song, Yang
前言：大肠癌是最常见的肿瘤之一，主要是因为肝转移的发生而致命。肌醇六磷酸（IP 6）和肌醇（INS）在体内外均具有抗肿瘤作用，但IP 6和INS联合应用的抗肿瘤效果优于IP 6或INS单独应用。IP 6的抑制作用，INS和IP 6+的组合在结直肠癌原位移植模型中研究INS对结直肠癌的肿瘤进展和肝转移的影响。通过体内生物发光成像选择荷瘤小鼠，并分别用IP 6、INS和IP 6与INS联合治疗。治疗6周后处死所有小鼠。比较各组肿瘤的发生、转移情况。结果：IP 6、INS、IP 6 + INS均能抑制肝癌细胞的肝转移，与MG组相比，IP6_G、INS_G、IP 6 +INS_G组的生存期延长，肿瘤重量减轻。此外，IP 6 +INS_G组小鼠肝转移面积相对小于M_G组、IP6_G组和INS_G组。RNA-seq分析结果显示，与M_G组相比，IP 6 +INS_G组Wnt 10 b、Tcf 7和c-Myc的表达明显下调（P
Introduction: Colorectal cancer, one of the most common tumors, is mainly fatal because of the occurrence of liver metastasis. Inositol hexaphosphate (IP6) and inositol (INS) were found, both, in vitro and in vivo to play an anti-tumor effect, whereas the combination of IP6 and INS was more effective than IP6 or INS alone.Materials and Methods: The inhibitory effects of IP6, INS and the combination of IP6 +INS on tumor progression and liver metastasis of colorectal cancer were investigated in an orthotopic transplantation model of colorectal cancer. The tumor-bearing mice were selected by in vivo bioluminescence imaging and were treated with IP6, INS, and IP6 combined with INS, respectively. All mice were sacrificed after 6 weeks of treatment. The cancer development and metastasis were compared among the groups. The expression of genes related to the Wnt/beta-catenin in the model was analyzed.Results: The results demonstrated that liver metastasis was inhibited after treatment with IP6, INS, and IP6+INS. Compared to that of the M_G, survival period was extended, and tumor weight was lowered in IP6_G, INS_G, and IP6+INS_G. Besides, the liver metastatic area of mice in IP6+INS_G was relatively smaller than that in M_G, IP6_G, or INS_G. The results of RNA-seq analysis showed that the expressions of Wnt10b, Tcf7, and c-Myc were significantly downregulated in IP6+INS_G compared to that inM_G (P