Sangeetha N, Nalini N
Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, Chidambaram, Tamil Nadu, India School of Chemical and Biotechnology, SASTRA University, Thirumalaisamudram, Thanjavur, Tamil Nadu, India.
Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, Chidambaram, Tamil Nadu, India
Hum Exp Toxicol. 2015 Jan;34(1):56-64. doi: 10.1177/0960327114530741. Epub 2014 Apr 16.
To authenticate the colon cancer preventive potential of silibinin, the efficacy of silibinin needs to be tested by evaluating an organ-specific biomarker. The aim of this study was to evaluate the impact of silibinin on the colonic expression of the caudal-type homeobox transcription factor (CDX2) an intestine specific tumor suppressor gene and its downstream targets in the colon of rats challenged with 1,2 dimethyl hydrazine (DMH). Rats of groups 1 and 2 were treated as control and silibinin control. Rats under groups 3 and 4 were given DMH (20 mg/kg body weight (b.w.) subcutaneously) once a week for 15 consecutive weeks from the 4th week of the experimental period. In addition, group 4 rats alone were treated with silibinin (50 mg/kg b.w. per os) everyday throughout the study period of 32 weeks. Histological investigation and messenger RNA and protein expression studies were performed in the colonic tissues of experimental rats. Findings of the study revealed that DMH administration significantly decreased the expression of CDX2 and Guanylyl cyclase C (GCC) in the colon of experimental rats. Further the decreased levels of CDX2 protein, colonic mucin content, and increased number of mast cells in the colon of DMH alone-administered rats reflects the onset of carcinogenesis. The pathological changes caused due to CDX2 suppression were attenuated by silibinin supplementation.
为验证水飞蓟宾对结肠癌的预防潜力，需要通过评估一种器官特异性生物标志物来测试水飞蓟宾的功效。本研究的目的是评估水飞蓟宾对尾型同源框转录因子（CDX2）在结肠中的表达的影响，CDX2是一种肠道特异性肿瘤抑制基因及其在接受1,2 - 二甲基肼（DMH）攻击的大鼠结肠中的下游靶点。第1组和第2组大鼠作为对照和水飞蓟宾对照进行处理。第3组和第4组大鼠从实验期第4周开始，每周皮下注射一次DMH（20 mg/kg体重），连续注射15周。此外，在整个32周的研究期间，仅第4组大鼠每天口服水飞蓟宾（50 mg/kg体重）。对实验大鼠的结肠组织进行了组织学研究以及信使核糖核酸和蛋白质表达研究。研究结果显示，给予DMH显著降低了实验大鼠结肠中CDX2和鸟苷酸环化酶C（GCC）的表达。此外，单独给予DMH的大鼠结肠中CDX2蛋白水平降低、结肠粘蛋白含量减少以及肥大细胞数量增加，反映了致癌作用的开始。补充水飞蓟宾减轻了因CDX2抑制引起的病理变化。
