Resveratrol inhibits the invasion and metastasis of colon cancer through reversal of epithelial-mesenchymal transition via the AKT/GSK-3β/Snail signaling pathway
Resveratrol inhibits the invasion and metastasis of colon cancer through reversal of epithelial-mesenchymal transition via the AKT/GSK-3β/Snail signaling pathway
复制标题
白藜芦醇通过AKT/GSK-3β/Snail信号通路逆转上皮间质转化抑制结肠癌的侵袭和转移
DOI：
10.3892/mmr.2019.10528
复制
发表时间：
2019-09-01
影响因子：
3.4
通讯作者：
Ruan, Shanming
中科院分区：
文献类型：
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作者：
Yuan, Li;Zhou, Mengmeng;Ruan, Shanming
为了改善结肠癌患者的临床结局，需要鉴定安全有效的抑制肿瘤侵袭和转移的药物。本研究旨在探讨白藜芦醇对结肠癌侵袭转移的抑制作用及其可能的作用机制。采用AKT 1基因敲低的SW 480和SW 620结肠癌细胞，检测白藜芦醇对细胞侵袭转移的影响，以及对上皮间质转化（EMT）标志物和丝氨酸/苏氨酸激酶（AKT）/糖原合成酶激酶（GSK）-3 β/Snail信号通路相关分子表达的影响。采用裸鼠尾静脉接种SW 480细胞建立结肠癌肺转移模型，观察白藜芦醇对结肠癌肺转移的影响。结果显示，白藜芦醇处理和AKT 1敲低显著抑制结肠癌细胞的迁移和侵袭，并显著增加E-钙粘蛋白的表达，降低N-钙粘蛋白，磷酸化（p）-AKT 1，p-GSK-3 β，和Snail在结肠癌中的体外和体内表达。此外，白藜芦醇的作用在AKT 1敲低细胞中明显较弱。结论：白藜芦醇可能通过AKT/GSK-3 β/Snail信号通路逆转EMT，从而抑制结肠癌的侵袭和转移。因此，AKT 1可能是结肠癌细胞中EMT的关键调节因子，也是这种疾病的潜在治疗靶点。
The identification of safe and effective drugs that inhibit tumor invasion and metastasis is required to improve the clinical outcome of patients with colon cancer. The present study aimed to investigate the inhibitory effects and possible mechanisms of action of resveratrol against the invasion and metastasis of colon cancer. AKT1-knockdown SW480 and SW620 colon cancer cells were used to detect the effects of resveratrol on cell invasion and metastasis, as well as changes in the expression of epithelial-mesenchymal transition (EMT) markers and serine/threonine kinase (AKT)/glycogen synthase kinase (GSK)-3 beta/Snail signaling pathway-related molecules in vitro. Furthermore, nude mice were inoculated with SW480 cells in the tail vein to establish an in vivo lung metastasis model of colon cancer, to investigate the effects of resveratrol on lung metastasis in colon cancer. The results revealed that resveratrol treatment and AKT1 knockdown significantly inhibited cell migration and invasion in colon cancer, and markedly increased E-cadherin expression and decreased that of N-cadherin, phospho (p)-AKT1, p-GSK-3 beta, and Snail in colon cancer both in vitro and in vivo. Furthermore, the effects of resveratrol were significantly weaker in the AKT1-knockdown cells. In conclusion, resveratrol may suppress the invasion and metastasis of colon cancer through reversal of EMT via the AKT/GSK-3 beta/Snail signaling pathway. AKT1 may therefore be a key regulator of EMT in colon cancer cells and a potential therapeutic target for this disease.