植酸对结直肠癌模型大鼠Wnt信号通路的影响

EFFECT OF PHYTIC ACID ON THE WNT SIGNALING PATHWAY IN A RAT MODEL OF COLORECTAL CANCER

目的通过建立结直肠癌大鼠模型探讨植酸在Wnt信号通路中对结直肠癌的调控机制。方法将60只Wistar大鼠随机分为对照组、模型组、植酸低剂量组、植酸中剂量组、植酸高剂量组。对照组和模型组大鼠每日用生理盐水灌胃,植酸低、中、高剂量组大鼠分别给予0.25、0.50、1.00g/kg体质量的植酸钠灌胃,灌胃4周后建立结直肠癌模型。实验期间记录各组大鼠体质量变化;实验最后观察大鼠结直肠癌发生情况,采用Western Blot法检测大鼠结直肠组织或肿瘤组织中Wnt通路相关蛋白磷酸化糖原合成酶激酶-3β(pGSK-3β)、活性β-链蛋白(activeβ-catenin)和细胞周期蛋白(CyclinD1)的表达,应用流式细胞术分析上述组织中细胞的周期变化。结果与模型组相比,经植酸干预的各组大鼠体质量下降较少,植酸中、高剂量组大鼠肿瘤发生率下降。与模型组相比,经植酸干预的各组大鼠pGSK-3β、activeβ-catenin和CyclinD1蛋白表达下降(F=5.400~13.534,P<0.05);S期细胞所占比例降低,细胞出现G1期停滞(F=4.268、28.467,P<0.05)。结论植酸可以通过抑制Wnt通路相关蛋白表达、调节细胞周期,从而达到抑制结直肠癌发生发展的作用,且抑制效果呈剂量依赖性。

Objective To determine the mechanism of action of phytic acid in regulating colorectal cancer cell cycle via the Wnt signaling pathway in a rat model of colorectal cancer. Methods Sixty Wistar rats were randomly assigned to control group,model group,low-dose phytic acid group,medium-dose phytic acid group,and high-dose phytic acid group.The control group and model group were given saline daily by gavage,while the three phytic acid groups were given sodium phytate daily at doses of 0.25,0.50,and 1.00g/kg body weight,respectively.After 4weeks of phytic acid administration,a rat model of colorectal cancer was established in the model group,low-dose phytic acid group,medium-dose phytic acid group,and high-dose phytic acid group.Changes in the body weight of rats in the five groups were recorded.Upon being sacrificed,tumor incidence in the five groups was analyzed based on the expression of Wnt signaling pathway-related proteins pGSK-3β,activeβ-catenin,and CyclinD1 in colorectal cancer or control tissues measured by Western Blot.Cell cycle in these tissues was also examined using flow cytometry.Results Compared with the model group,rats in the phytic acid-treated groups had less body weight loss,and the colorectal cancer incidence was also reduced in the medium-and high-dose phytic acid groups.The protein expression of pGSK-3β,activeβ-catenin,and CyclinD1 was progressively reduced with phytic acid administration in a dose-dependent manner（F=5.400-13.534,P〈0.05）.Cell reduction in the S phase and cell arrest in the G1 phase were also observed in the tumor cells after phytic acid treatment（F=4.268,28.467;P〈0.05）. Conclusion Phytic acid can inhibit the expression of Wnt signaling pathway-related proteins and regulate tumor cell cycle to reduce the incidence of colorectal cancer in a dose-dependent manner.