生酮饮食对人肺癌细胞裸鼠皮下移植瘤生长的影响

doi:10.3969/j.issn.1004-616x.2020.04.007

癌变·畸变·突变 ›› 2020, Vol. 32 ›› Issue (4): 286-291.doi: 10.3969/j.issn.1004-616x.2020.04.007

生酮饮食对人肺癌细胞裸鼠皮下移植瘤生长的影响

张凡¹, 刘广超², 张之晗¹, 刘方芳¹, 谢琪¹, 高淑清¹

1. 河北医科大学第四医院营养科, 河北石家庄 050011;
2. 中国人民解放军联勤保障部队第980医院普通外科, 河北石家庄 050011

收稿日期:2020-04-17 修回日期:2020-06-17 出版日期:2020-07-31 发布日期:2020-08-01
通讯作者: 高淑清,E-mail:656720571@qq.com E-mail:656720571@qq.com
作者简介:张凡,E-mail:471778194@qq.com。
基金资助:
国家癌症中心肿瘤科研专项课题（NCC2017A27）

Effect of ketogenic diet on growth of subcutaneously transplanted human lung cancer in nude mice

ZHANG Fan¹, LIU Guangchao², ZHANG Zhihan¹, LIU Fangfang¹, XIE Qi¹, GAO Shuqing¹

1. Department of Nutrition, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050011;
2. Department of General Surgery, No. 980 Hospital of Joint Logistic Support Force of People's Liberation Army of China, Shijiazhuang 050011, Hebei, China

Received:2020-04-17 Revised:2020-06-17 Online:2020-07-31 Published:2020-08-01

摘要/Abstract

摘要： 目的： 建立人肺癌细胞裸鼠皮下移植瘤模型，观察生酮饮食对裸鼠皮下移植瘤生长的影响并对其作用机制进行研究。方法： 10只雌性BALB/c裸鼠右下肢皮下注射人肺癌A549细胞，建立肺癌细胞裸鼠移植瘤模型后，随机分为标准饮食组（SD组）和生酮饮食组（KD组），分组当天测量裸鼠体质量、移植瘤体积、血糖及血酮浓度，以后每5 d测量1次。接种肿瘤细胞后第30天，摘眼球取血处死裸鼠，取血后进行血脂四项检测。剥离移植瘤组织，分别采用Western blot及免疫组织化学方法检测裸鼠移植瘤组织中4-HNE蛋白的表达水平。结果： 接种肿瘤细胞后第15天起，KD组裸鼠血酮浓度较SD组升高，血糖浓度较SD组降低，差异均有统计学意义（P < 0.05）。接种肿瘤细胞后第20天起，KD组裸鼠体质量及移植瘤体积小于SD组，差异均有统计学意义（P < 0.05）。接种肿瘤细胞后第30天，KD组裸鼠的总胆固醇（CHOL）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）浓度高于SD组，甘油三酯（TG）浓度低于SD组，差异均有统计学意义（P < 0.05）。Western blot法分析结果显示KD组裸鼠移植瘤组织中4-HNE蛋白相对表达水平（1.45±0.10）高于SD组（1.00±0.03），差异有统计学意义（P < 0.05）。免疫组化法检测结果显示KD组裸鼠移植瘤组织中4-HNE表达水平（4.40±0.89）高于SD组（2.40±0.89），差异有统计学意义（P < 0.05）。结论： 生酮饮食可以抑制人肺癌细胞裸鼠皮下移植瘤的生长，其作用机制可能与肿瘤细胞氧化应激的增强有关。

关键词: 生酮饮食, 肺癌, 裸鼠, 4-羟基壬烯醛

Abstract: OBJECTIVE: To establish a subcutaneously transplanted tumor model of human lung cancer in nude mice and to evaluate effect of ketogenic diet on growth of the subcutaneously transplanted tumor. METHODS: Human lung cancer A549 cells were subcutaneously injected into the right lower limb of 10 female BALB/c nude mice. After establishing the transplanted tumor model, the nude mice were randomly divided into a standard diet group (standard diet,SD group) and a ketogenic diet group (ketogenic diet,KD group). Body mass,tumor volume,blood glucose and blood ketone concentration of nude mice were measured on the same day,and then every 5 days. On the 30th day after inoculation,the nude mice were killed,and blood lipids were determined from blood samples taken from their eyes. The transplanted tumor tissue was stripped, and the protein expression level of 4-HNE in the transplanted tumor tissue of nude mice was detected by Western blot and immunohistochemistry. RESULTS: From the 15th day after inoculation, the blood ketone concentration in the KD group was higher than that in the SD group, and the blood glucose concentration in the SD group was lower (P < 0.05). From the 20th day after inoculation,the body weight and tumor volume of the KD nude mice were significantly smaller than those in the SD group (P < 0.05). On the 30th day after inoculation, the concentration of total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C),and low-density lipoprotein cholesterol (LDL-C) in the KD nude mice were higher than those in SD group,and the concentration of triglyceride (TG) were lower than SD. The difference between the two groups was statistically significant (P < 0.05). Western blot results showed that the relative expression level of 4-HNE in the KD group (1.45±0.10) was significantly higher than that in the SD group (1.00±0.03) (P < 0.05). Immunohistochemical results showed that the expression level of 4-HNE in the KD group (4.40±0.89) was significantly higher than that in the SD group (2.40±0.89) (P < 0.05). CONCLUSION: KD diet inhibited the growth of subcutaneously transplanted human lung cancer in nude mice,and its mechanism may be related to the enhancement of oxidative stress of tumor cells.

Key words: ketogenic diet, lung cancer, nude mice, 4-hydroxynonenal

中图分类号:

R730.59

张凡, 刘广超, 张之晗, 刘方芳, 谢琪, 高淑清. 生酮饮食对人肺癌细胞裸鼠皮下移植瘤生长的影响[J]. 癌变·畸变·突变, 2020, 32(4): 286-291.

ZHANG Fan, LIU Guangchao, ZHANG Zhihan, LIU Fangfang, XIE Qi, GAO Shuqing. Effect of ketogenic diet on growth of subcutaneously transplanted human lung cancer in nude mice[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(4): 286-291.

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生酮饮食对人肺癌细胞裸鼠皮下移植瘤生长的影响

Effect of ketogenic diet on growth of subcutaneously transplanted human lung cancer in nude mice

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