Science:高果糖玉米糖浆促进小鼠肠道肿瘤生长 诸平 美国/瑞士以及韩国的研究人员合作研究发现含葡萄糖(Glu)和果糖(Fru)混合物的加糖饮料(SSBs)，在饮用后通过胃肠道。 Marcus D. Goncalves 等人的研究表明，Glu和Fru被肠道肿瘤直接吸收，每天服用SSBs可以加速肿瘤的生长。这种生长促进作用依赖于酮己糖激酶(KHK)，它从Fru中产生果糖1-磷酸酯(F1P)，导致三磷酸腺苷(ATP)的耗竭。这两种代谢变化都促进Glu转化为肿瘤生长所需的构建块。 糖是否直接喂养癌症，促进它们的生长?贝勒医学院(Baylor College of Medicine)和威尔康奈尔医学院(Weill Cornell Medicine)的研究人员牵头进行的一项研究显示，至少在老鼠身上，答案似乎是肯定的。他们的研究结果于2019年3月22日在《科学》（Science）杂志网站上发表（ 1345.full.pdf ），研究表明，每天摄入适量的高果糖玉米糖浆——相当于人们每天喝大约12盎司的含糖饮料——会加速这种疾病小鼠模型中肠道肿瘤的生长，而与肥胖无关。研究小组还发现了饮用含糖饮料可以直接促进癌症生长的机制，这表明了潜在的新型治疗策略。更多信息请注意浏览原文或者相关报道。 High-fructose corn syrup boosts intestinal tumor growth in mice Does sugar directly feed cancers, boosting their growth? The answer seems to be 'Yes' at least in mice according to a study led by researchers at Baylor College of Medicine and Weill Cornell Medicine. Their study, published ... Does sugar directly feed cancers, boosting their growth? The answer seems to be 'Yes' at least in mice according to a study led by researchers at Baylor College of Medicine and Weill Cornell Medicine. Their study, published in Science , showed that consuming a daily modest amount of high-fructose corn syrup—the equivalent of people drinking about 12 ounces of a sugar-sweetened beverage daily—accelerates the growth of intestinal tumors in mouse models of the disease, independently of obesity. The team also discovered the mechanism by which the consumption of sugary drinks can directly feed cancer growth, suggesting potential novel therapeutic strategies. An increasing number of observational studies have raised awareness of the association between consuming sugary drinks , obesity and the risk of colorectal cancer , said co-corresponding author Dr. Jihye Yun, assistant professor of molecular and human genetics at Baylor. The current thought is that sugar is harmful to our health mainly because consuming too much can lead to obesity. We know that obesity increases the risk of many types of cancer including colorectal cancer; however, we were uncertain whether a direct and causal link existed between sugar consumption and cancer. Therefore, I decided to address this important question when I was a postdoc in the Dr. Lewis Cantley lab at Weill Cornell Medicine. First, Yun and her colleagues generated a mouse model of early-stage colon cancer where APC gene is deleted. APC is a gatekeeper in colorectal cancer. Deleting this protein is like removing the breaks of a car. Without it, normal intestinal cells neither stop growing nor die, forming early stage tumors called polyps. More than 90 percent of colorectal cancer patients have this type of APC mutation, Yun said. Using this mouse model of the disease, the team tested the effect of consuming sugar-sweetened water on tumor development. The sweetened water was 25 percent high-fructose corn syrup, which is the main sweetener of sugary drinks people consume. High-fructose corn syrup consists of glucose and fructose at a 45:55 ratio. When the researchers provided the sugary drink in the water bottle for the APC-model mice to drink at their will, mice rapidly gained weight in a month. To prevent the mice from being obese and mimic humans' daily consumption of one can of soda, the researchers gave the mice a moderate amount of sugary water orally with a special syringe once a day. After two months, the APC-model mice receiving sugary water did not become obese, but developed tumors that were larger and of higher-grade than those in model mice treated with regular water. These results suggest that when the animals have early stage of tumors in the intestines—which can occur in many young adult humans by chance and without notice—consuming even modest amounts of high-fructose corn syrup in liquid form can boost tumor growth and progression independently of obesity, Yun said. Further research is needed to translate these discovery to people; however, our findings in animal models suggest that chronic consumption of sugary drinks can shorten the time it takes cancer to develop. In humans, it usually takes 20 to 30 years for colorectal cancer to grow from early stage benign tumors to aggressive cancers. This observation in animal models might explain why increased consumption of sweet drinks and other foods with high sugar content over the past 30 years is correlating with an increase in colorectal cancers in 25 to 50-year-olds in the United States, said Cantley, co-corresponding author, former mentor of Yun and professor of cancer biology in medicine and director of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. Mute Settings Enter fullscreen The team then investigated the mechanism by which this sugar promoted tumor growth. They discovered that the APC-model mice receiving modest high-fructose corn syrup had high amounts of fructose in their colons. We observed that sugary drinks increased the levels of fructose and glucose in the colon and blood, respectively and that tumors could efficiently take up both fructose and glucose via different routes. Using cutting-edge technologies to trace the fate of glucose and fructose in tumor tissues, the team showed that fructose was first chemically changed and this process then enabled it to efficiently promote the production of fatty acids, which ultimately contribute to tumor growth. Most previous studies used either glucose or fructose alone to study the effect of sugar in animals or cell lines. We thought that this approach did not reflect how people actually consume sugary drinks because neither drinks nor foods have only glucose or fructose. They have both glucose and fructose together in similar amounts, Yun said. Our findings suggest that the role of fructose in tumors is to enhance glucose's role of directing fatty acids synthesis. The resulting abundance of fatty acids can be potentially used by cancer cells to form cellular membranes and signaling molecules, to grow or to influence inflammation. To determine whether fructose metabolism or increased fatty acid production was responsible for sugar-induced tumor growth, the researchers modified APC-model mice to lack genes coding for enzymes involved in either fructose metabolism or fatty acid synthesis. One group of APC-model mice lacked an enzyme KHK, which is involved in fructose metabolism, and another group lacked enzyme FASN, which participates in fatty acid synthesis. They found that mice lacking either of these genes did not develop larger tumors, unlike APC-model mice, when fed the same modest amounts of high-fructose corn syrup. This study revealed the surprising result that colorectal cancers utilize high-fructose corn syrup , the major ingredient in most sugary sodas and many other processed foods, as a fuel to increase rates of tumor growth, Cantley said. While many studies have correlated increased rates of colorectal cancer with diet, this study shows a direct molecular mechanism for the correlation between consumption of sugar and colorectal cancer. Our findings also open new possibilities for treatment, Yun said. Unlike glucose, fructose is not essential for the survival and growth of normal cells, which suggests that therapies targeting fructose metabolism are worth exploring. Alternatively, avoiding consuming sugary drinks as much as possible instead of relying on drugs would significantly reduce the availability of sugar in the colon. While further studies in humans are necessary, Yun and colleagues hope this research will help to raise public awareness about the potentially harmful consequences consuming sugary drinks has on human health and contribute to reducing the risk and mortality of colorectal cancer worldwide.
MiR-124 retards bladder cancer growth by directly targeting CDK4 Ting Zhang, Jingyao Wang, Xiaofeng Zhai, Hongjie Li, Changying Li and Jiwu Chang Acta Biochim Biophys Sin 2014, Dec, 46(12): 1072–1079; doi: 10.1093/abbs/gmu105 Tianjin Institute of Urology, Second Hospital of Tianjin Medical University, Tianjin 300211, China MicroRNAs (miRNAs) are a class of non-coding small RNAs that act as negative regulators of gene expression by binding to the 3′-untranslated region (3′UTR) of target mRNAs. In order to investigate the physiological role of miR-124 in bladder cancer, target genes of miR-124 were predicted by the TargetScan software, and cyclin-dependent kinase (CDK4), which has been implicated as a regulator of cell cycle, was chosen for further study. MiR-124 could significantly repress CDK4 expression by targeting its binding site in the 3′UTR of CDK4 in vitro. In both bladder cancer cell lines and tissues, the expression of miR-124 was significantly down-regulated, while CDK4 expression was up-regulated. Ectopic expression of miR-124 in transplanted HT1197 cells resulted in the retardation of tumor growth in mouse tumor xenografts. And the expression of miR-124 and CDK4 showed an obvious inverse correlation in these xenograft tissues, which was also observed in human bladder cancer tissue samples. Taken together, our results strongly suggest that miR-124 can arrest cell cycle and restrain the growth of bladder cancer by targeting CDK4 directly. 图例: miR-124高表达对肿瘤生长的影响 全文: http://abbs.oxfordjournals.org/content/46/12/1072.full
标签: 肿瘤生长
