Inositol hexaphosphate suppresses colorectal cancer cell proliferation via the Akt/GSK-3β/β-catenin signaling cascade in a 1,2-dimethylhydrazine-induced rat model
Inositol hexaphosphate suppresses colorectal cancer cell proliferation via the Akt/GSK-3β/β-catenin signaling cascade in a 1,2-dimethylhydrazine-induced rat model
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在 1,2-二甲基肼诱导的大鼠模型中，肌醇六磷酸通过 Akt/GSK-3 beta/beta-catenin 信号级联抑制结直肠癌细胞增殖
DOI：
10.1016/j.ejphar.2017.03.011
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发表时间：
2017-06-15
影响因子：
5
通讯作者：
Song，Yang
中科院分区：
文献类型：
--
作者：
Yu，Wenyang;Liu，Cuiping;Song，Yang
结直肠癌（CRC）在世界范围内很常见，大多数CRC治疗都有不良副作用。许多研究表明，肌醇六磷酸（IP 6）对结直肠癌有较强的抗癌活性，对正常细胞无明显毒性。然而，其内在机制尚不清楚。在这项研究中，我们研究了IP 6在CRC中的抗癌和抗增殖特性及其在此化学预防过程中的可能机制。我们研究了IP 6给药后DMH诱导的大鼠CRC模型中与PI 3 K/Akt和Wnt通路相关的基因在转录和翻译水平上的表达。此外，我们还进行了细胞增殖分析。结果表明，IP 6对DMH诱导的大鼠肿瘤的发生率、肿瘤数量、肿瘤重量和肿瘤体积均有抑制作用。此外，Akt和c-Myc mRNA水平显著降低。IP 6还显示出下调Akt、pAkt、pGSK-3β和c-Myc蛋白表达，并上调pβ-连环蛋白表达。此外，来自IP 6处理的大鼠的肿瘤组织显示出增殖降低。总之，IP 6的抗增殖作用可能与PI 3 K/Akt和Wnt通路之间的串扰有关，揭示了IP 6在我们的模型中抑制CRC的潜在机制。
Colorectal cancer (CRC) is common worldwide, and most treatments for CRC have undesirable side effects. Many researchers have demonstrated that inositol hexaphosphate (IP6) has potent anticarcinogenic activity against CRC and no apparent toxicity to normal cells. However, the underlying mechanism is still unclear. In this study, we investigated the anticancer and anti-proliferative properties of IP6 in CRC and its possible mechanisms during this chemopreventive process. We examined the expression of genes related to the PI3K/Akt and Wnt pathways at the transcriptional and translational levels in a DMH-induced rat CRC model following IP6 administration. In addition, we also conducted cell proliferation analysis. The results demonstrated that IP6 could inhibit tumors, in terms of tumor incidence, number, weight and volume in DMH-induced rats. Additionally, Akt and c-Myc mRNA levels were significantly decreased. IP6 was also shown to downregulate Akt, pAkt, pGSK-3β, and c-Myc protein expression and upregulate pβ-catenin protein expression. Furthermore, tumor tissues from IP6-treated rats showed decreased proliferation. In conclusion, the anti-proliferative effect of IP6 may be related to crosstalk between the PI3K/Akt and Wnt pathways, revealing a potential mechanism of CRC inhibition by IP6 in our model.