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

Abstract

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

CLC Number:

R730.59

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.

References

[1] LU Z L, GUO Y K, ZHANG X Y, et al. ORY-1001 suppresses cell growth and induces apoptosis in lung cancer through triggering HK2 mediated Warburg effect[J]. Front Pharmacol, 2018, 9:1411.
[2] WISHART D S. Is cancer a genetic disease or a metabolic disease?[J]. EBioMedicine, 2015, 2(6):478-479.
[3] WARBURG O, WIND F, NEGELEIN E. The metabolism of tumors in the body[J]. J Gen Physiol, 1927, 8(6):519-530.
[4] SHOEB M, ANSARI N H, SRIVASTAVA S K, et al. 4-Hydroxynonenal in the pathogenesis and progression of human diseases[J]. Curr Med Chem, 2014, 21(2):230-237.
[5] 陈良才, 陈纪涛, 冯笑, 等. 生酮饮食抑制人肺癌裸鼠皮下移植瘤生长及其机制研究[J]. 实用医学杂志, 2016, 32(22):3661-3664.
[6] 田艳, 冼乐武. 生酮饮食对人肺癌裸鼠皮下移植瘤的作用和相关机制研究[J]. 广东医学, 2018, 39(5):670-674.
[7] 石汉平. 肿瘤生酮疗法[J]. 肿瘤代谢与营养电子杂志, 2016, 3(2):66-70.
[8] SAMALA R, KLEIN J, BORGES K. The ketogenic diet changes metabolite levels in hippocampal extracellular fluid[J]. Neurochem Int, 2011, 58(1):5-8.
[9] SCHIFF M, BéNIT P, COULIBALY A, et al. Mitochondrial response to controlled nutrition in health and disease[J]. Nutr Rev, 2011, 69(2):65-75.
[10] ZUCCOLI G, MARCELLO N, PISANELLO A, et al. Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet:Case report[J]. Nutr Metab (Lond), 2010, 7:33.
[11] FREEDLAND S J, MAVROPOULOS J, WANG A, et al. Carbohydrate restriction, prostate cancer growth, and the insulin-like growth factor Axis[J]. Prostate, 2008, 68(1):11-19.
[12] MASKO E M, THOMAS J A, ANTONELLI J A, et al. Low-carbohydrate diets and prostate cancer:how low is "low enough"?[J]. Cancer Prev Res, 2010, 3(9):1124-1131.
[13] ZHOU W H, MUKHERJEE P, KIEBISH M A, et al. The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer[J]. Nutr Metab (Lond), 2007, 4:5.
[14] 郝光伟, 王海玉, 何德明, 等. 生酮饮食对人结肠癌裸鼠皮下移植瘤生长的影响[J]. 中国肿瘤临床, 2014, 41(18):1154-1157.
[15] ALLEN B G, BHATIA S K, BUATTI J M, et al. Ketogenic diets enhance oxidative stress and radio-chemo-therapy responses in lung cancer xenografts[J]. Clin Cancer Res, 2013, 19(14):3905-3913.
[16] 刘润奇, 刘民锋, 蒋笑晨, 等. 生酮饮食对小鼠EMT-6乳腺癌生长影响的实验研究[J]. 中华肿瘤防治杂志, 2015, 22(11):827-831.
[17] AGGARWAL A, YUAN Z L, BARLETTA J A, et al. Ketogenic diet combined with antioxidant N-acetylcysteine inhibits tumor growth in a mouse model of anaplastic thyroid cancer[J]. Surgery, 2020, 167(1):87-93.
[18] OTTO C, KAEMMERER U, ILLERT B, et al. Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with Omega-3 fatty acids and medium-chain triglycerides[J]. BMC Cancer, 2008, 8:122.
[19] FATH M A, DIERS A R, AYKIN-BURNS N, et al. Mitochondrial Electron transport chain blockers enhance 2-deoxy-D-glucose induced oxidative stress and cell killing in human colon carcinoma cells[J]. Cancer Biol Ther, 2009, 8(13):1228-1236.
[20] TRACHOOTHAM D, ZHOU Y, ZHANG H, et al. Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by beta-phenylethyl isothiocyanate[J]. Cancer Cell, 2006, 10(3):241-252.
[21] NOGUEIRA V, PARK Y, CHEN C C, et al. Akt determines replicative senescence and oxidative or oncogenic premature senescence and sensitizes cells to oxidative apoptosis[J]. Cancer Cell, 2008, 14(6):458-470.
[22] RAY P D, HUANG B W, TSUJI Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling[J]. Cell Signal, 2012, 24(5):981-990.
[23] GORRINI C, HARRIS I S, MAK T W. Modulation of oxidative stress as an anticancer strategy[J]. Nat Rev Drug Discov, 2013, 12(12):931-947.
[24] SPORN M B, LIBY K T. NRF2 and cancer:the good, the bad and the importance of context[J]. Nat Rev Cancer, 2012, 12(8):564-571.
[25] ALBRIGHT C D, KLEM E, SHAH A A, et al. Breast cancer cell-targeted oxidative stress:enhancement of cancer cell uptake of conjugated linoleic acid, activation of p53, and inhibition of proliferation[J]. Exp Mol Pathol, 2005, 79(2):118-125.

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

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	LIU Xiaoxia, LI Weixia, LI Zhijia, SU Zhenjun, DUAN Xiaohui, HAN Weiwen, WANG Yunxiao, HE Xiaolei, Lu Linlin, JIA Jinhai. Correlations between glutathione peroxidase in serum and clinicopathological outcomes of advanced non-small cell lung cancer [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(4): 286-290,295.
[2]	WANG Xikai, MENG Qinghe, GAO Yanlu. miR-223-3p negatively regulated ECT2 to induce apoptosis in non-small cell lung cancer cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(3): 187-192.
[3]	ZHAO Junwei, HUA Chenfeng, SHANG Pingping, XIE Fuwei, LI Xiang. Induction of oxidative stress by arsenious acid As(Ⅲ) in A549 cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(1): 28-31.
[4]	LIU Xiaoxia, LI Weixia, SU Zhenjun, JIA Jinhai, DUAN Xiaohui, LI Zhijia, HE Xiaolei, L Linlin, LIU Rui, WANG Yunxiao. Analyses of clinicopathological characteristics and curative effect of combined radio-with chemo-therapy for advanced non-small cell lung cancer with superoxide dismutase activity in serum [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(5): 350-354.
[5]	YING Wei, WANG Xingyuan, JIANG Bo, ZHOU Wei. Association between polymorphisms in the miR-146a and susceptibility to non-small cell lung cancer [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(3): 222-226.
[6]	ZHU Jiawei, HU Xiao, WANG Xijun, WANG Yaru, FENG Lin, XIAO Ting. Clinical significance of Skp1 protein expression in non-small cell lung cancer tissues and peripheral blood [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(2): 89-95.
[7]	WU Wen, LI Ping, ZUO Ran, ZENG Qingbo, WU Desheng, XIE Ni, LONG Dingxin, YUAN Jianhui. Correlation between polymorphism of DNA methyltransferase 3B-149C>T and cancer risk:a meta-analysis [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(2): 102-110.
[8]	MA Bangjing, HAO Xianglin, HAN Fei, CHEN Hongqiang, LIU Jinyi, CAO Jia, ZHANG Aihua. Inhibition of proliferation and migration of lung adenocarcinoma cells by SOX30 gene via regulation of DSC3 gene [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2018, 30(3): 165-170,175.
[9]	WU Yilan, WANG Han. Inhibition of proliferation by resveratrol in paclitaxel-resistant lung adenocarcinoma cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2018, 30(3): 200-203,208.
[10]	WU Jianbin, JIANG Mei, WANG Yue, XU Jing, YUE Wentao, WANG Zitong. Comparison of patient-derived non-small cell lung cancer xenegrafts models in NOD/SCID and nude mice [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2018, 30(2): 114-119.
[11]	PENG Hui, MA Shumei, HONG Weiwei, SUI Jing, ZHANG Yanqiu, LIANG Geyu. Regulatory mechanism of miR-202 on proliferation of A549 lung cancer cells [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2017, 29(6): 454-459.
[12]	ZHANG Jing, TENG Yu, ZHAO Xiaoting, JIANG Mei, YUE Wentao. Effects of the inhibitor of Wnt production 2 on cell migration and invasion in non-small cell lung cancer [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2017, 29(4): 245-250.
[13]	SONG Jie, LI Ping, YU Xuexin, FENG Lin, GAO Yanning, XIAO Ting. Expression of Syntenin in non-small cell lung cancer tissues and its relationship with overall survival of patients [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2017, 29(2): 102-105.
[14]	XIAO Sha, ZHAO Xiujuan, KUANG Shicheng, LIU Yunru, LONG Wenfang, YANG Jianjun, HUANG Hairong. A Meta-analysis of the relationship between XPD 751 gene polymorphism and lung cancer [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2016, 28(4): 292-297.
[15]	ZHAI Xiaoran, JIANG Mei, ZHAO Xiaoting, GU Meng, YUE Wentao. Clinical significance of PFTK1 expression in human non-small cell lung cancer [J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2016, 28(3): 231-235.