RAS/MAPK/NF-κB信号通路在姜黄素治疗大鼠结肠癌中的作用

Role of RAS/MAPK/NF-κB signaling pathway in curcumin treatment of colon cancer in rats

目的:研究RAS/MAPK/NF-κB信号通路在姜黄素治疗大鼠结肠癌中的作用和意义。方法:大鼠结肠癌模型构建后,模型组和对照组给予正常饲料喂养,实验组给予0.2%姜黄素固体饲料喂食。HE染色观察结肠组织形态;检测结肠组织内EGFR蛋白;Western blot法和RT-PCR检测K-RAS、p-ERK、NF-κB、EGFR和Caspase 3蛋白含量和mRNA含量的表达。结果:与模型组相比,实验组大鼠结肠内肿瘤数目明显降低,差异有统计学意义(t=6.217,P<0.001)。模型组大鼠结肠癌诱癌率为85.00%,实验组大鼠为55.00%,差异有统计学意义(χ~2=4.286,P=0.038)。与对照组相比,模型组和实验组大鼠K-RAS、p-ERK、NF-κB、EGFR和Caspase 3 mRNA和蛋白含量显著升高,差异有统计学意义(P<0.05);与模型组相比,实验组大鼠K-RAS、p-ERK、NF-κB、EGFR和Caspase 3 mRNA和蛋白含量显著降低,差异有统计学意义(P<0.05)。结论:RAS/MAPK/NF-κB信号通路在姜黄素抑制结肠癌细胞的生长和增殖的过程中发挥重要作用。

Objective： To investigate the role and significance of RAS/MAPK/NF-κB signaling pathway in the treatment of colon cancer by curcumin. Methods： After colon cancer model was established in rats, The model group and the control group were fed with normal feed, and the experimental group was fed with 0.2% curcumin solid feed. The morphology of colon tissue was observed by HE staining. Immunohistochemistry was used to detect the expression of EGFR protein in colon tissues. Western blot and Real-time PCR were used to detect the expression of protein and mRNA of K-RAS, p-ERK, NF-κB, EGFR and Caspase 3. Results： Compared with the model group, the number of colonic tumors in the experimental group was significantly decreased, the difference was statistically significant（t=6.217, P〈0.001）. Compared with the model group, the cancer-inducing rate of colon cancer was 85.00%. The induced rate of colon cancer in experimental group was 55.00%, significantly lower than model group（χ2=4.286, P=0.038）. Compared with the control group, the mRNA and protein expressions of K-RAS, p-ERK, NF-κB, EGFR and Caspase 3 in model group and experimental group were significantly increased（P〈0.05）. The mRNA and protein expressions of K-RAS, p-ERK, NF-κB, EGFR and Caspase 3 in the experimental group were significantly lower than those in the untreated group（P〈0.05）. Conclusion： RAS/MAPK/NF-κB signaling pathway plays an important role in curcumin inhibiting and treating colon cancer cell growth and proliferation.