结直肠癌(colorectal cancer,CRC)是结肠和直肠粘膜上皮在环境或遗传等致癌因素作用下发生的恶性病变。高脂、高能量、低纤维膳食、久坐不动的生活方式及肥胖等都是CRC的危险因素。Sporamin蛋白是甘薯块根中特有的一种胰蛋白酶抑制剂,具有抑制脂肪细胞分化和降低CRC细胞血管内皮生长因子和基质金属蛋白酶表达的作用。近年来,胰岛素样生长因子(insulin-like growth factors,IGFs)家族信号分子在肥胖及CRC发展过程中的作用引起了人们的重视。肥胖可导致IGF结合蛋白基因甲基化,并引起IGF1、IGF2等促癌因子分泌增多。反之,限制热量、减肥和增加体力活动则能逆转IGFs通路信号分子的不利改变,产生抑癌作用。本文分析了甘薯sporamin蛋白抑制CRC的可能机制,并将重点放在IGFs通路信号分子所起的作用上,为进一步阐明sporamin蛋白抗CRC的作用机制提出了新的研究方向。
Colorectal cancer (CRC) is a malignance of the colon and rectal epithelium that usually occurs in the presence of a variety of environmental carcinogens and genetic factors. The high-fat, high-energy, low-fiber diet, the sedentary life style and obesity are the risk factors of CRC. Sporamin is a unique protein that is contained in the tuberous roots of sweet potato and is a kind of trypsin inhibitor. It has been shown to be able to inhibit the differentiation of preadipocyte and reduce the gene expression of vascular endothelial growth factor and matrix metalloproteinases in CRC cell lines. In recent years, signaling molecules of the insulin-like growth factor family (IGFs) and their role in the development of obesity and CRC have attracted much attention. Obesity has been shown to be able to lead to the methylation of IGFBP gene and increase the secretion of IGF1 and IGF2, resulting in tumor promotion. On the contrary, calorie restriction, weight loss and physical activity have been reported to be able to reverse the adverse changes in IGFs signaling molecules and result in a tumor suppression effect. In this review, the mechanism of action by which the sporamin protein inhibits the development of CRC is analyzed, with an emphasis on the possible role played by the IGFs. As a result, new research direction for the clarification of the mechanism of action by which the sporamin inhibits the development of CRC is proposed.