生酮饮食抑制人肺癌裸鼠皮下移植瘤生长及其机制研究  

Mechanism and inhibition effect of ketogenic diet on lung cancer xenografted nude mice

作　　者：陈良才[1] 陈纪涛[1] 冯笑[1] 刘浩[2] 刘季芳[1] 方向明[1] 易高[1] 

机构地区：[1]广州医科大学附属第五医院,广州市510700 [2]广州医科大学附属肿瘤医院肿瘤研究所,广州市510095

出　　处：《实用医学杂志》2016年第22期3661-3664,共4页The Journal of Practical Medicine

基　　金：广东省医学科研基金(编号:A2015234);广东省优秀青年教师项目(编号:B158030)

摘　　要：目的:研究生酮饮食对人肺癌裸鼠皮下移植瘤生长的影响及机制。方法:20只雌性BALB/C裸鼠皮下注射人肺癌A549细胞,随机均分为标准饮食组(SD组)和生酮饮食组(KD组)。1个月后,测量体重、瘤重、肿瘤体积;检测血糖和血酮体;对肿瘤、肺、肝脏、脑和心采用HE染色;IHC检测肿瘤组织中Ki-67、AMPK、p-AMPK和p-mTOR蛋白表达。结果:两组体重无显著差异(P>0.05);第10、25、30天KD组肿瘤体积明显变小(P<0.05),其中第25天尤其显著(P<0.01),抑瘤率为36%;与SD组相比,第30天KD组血糖降低(P<0.05);第10、20、30天KD组血酮上调(P<0.05),其中第20、30天更为显著(P<0.01);HE染色显示KD组肿瘤组织坏死面积显著增加,其他脏器无明显差异;免疫组化结果显示KD组肿瘤组织Ki-67和p-mTOR蛋白表达下降(P<0.05),p-AMPK表达上调(P<0.01),而AMPK蛋白表达无明显差异。结论:生酮饮食可明显抑制人肺癌裸鼠皮下移植瘤的生长,其抗癌作用可能与AMPK/mTOR信号通路的激活有关。Objective To investigate the effect of ketogenic diet on the growth of human lung cancer cells in nude mice and to clarify its possible mechanism. Methods Twenty female BALB/C nude mice injectedsubcutaneously with the tumor cells of the lung cancer cell line A549 were randomLy divided into standard diet group （SD group） and ketogenic diet group （KD group） and fed with two kinds of diet for 30d. Body weight, tumor weight and volume, blood sugar and blood ketone were measured 1 month later. The pathological changes of tumor, lung, liver, brain and heart were observed by HE staining. The expression of Ki67, AMPK, p-AMPK and p-mTOR were detected by immunohistochemical staining. Results The body weight of two groups had no statistically significant difference. The tumor volume of KD group was decreased significantly at the 10th, 25th and 30th day （P 〈 0.05） and the difference at the 25th day was especially distinct. The inhibition rate of tumor between two groups was 36%. Compared with that in SD group, the blood sugar in KD group was decreased sig- nificantly at the 30th day （P 〈 0.05）. However, the blood ketone in KD group was significant higher than that in SD group at thelOth, 20th and 30th day （P 〈 0.05） and the difference in both groups was especially obvious at 20th and 30th day; HE staining showed that the necrosis area of tumor tissue in KD group was larger than that in SD group but there was no obvious change in other organs; IHC showed that the expression of Ki67 and p-mTOR in KD group was lower significantly （P 〈 0.05）. However, the expression of p-AMPK was obviously increased （P 〈 0.01 ）. The expression of AMPK showed no significant difference between two groups. Conclu- sions The ketogenic diet can inhibit the nude mouse lung cancer xenograft growth and its anti-cancer effect may be related to the activation of AMPK/mTOR signaling pathways.

关 键 词：肺肿瘤 生酮饮食 AMPK/mTOR通路 

分 类 号：R734.2[医药卫生—肿瘤]