Ketogenic Diet Elicits Antitumor Properties through Inducing Oxidative Stress, Inhibiting MMP-9 Expression, and Rebalancing M1/M2 Tumor-Associated Macrophage Phenotype in a Mouse Model of Colon Cancer.
机构：[1]Institute of Biopharmaceutical Research, Liaocheng University, Liaocheng 252059, China[2]Key Laboratory for Pediatrics of Integrated Traditional and Western Medicine, Liaocheng People’s Hospital, Liaocheng 252059, China[3]Department of Clinical Nutrition Laboratory, Liaocheng People’s Hospital, Liaocheng 252059, China[4]RI-B-NT-Research Institute of Bioinformatics and Nanotechnology, Kiel 24118, Germany[5]Department of Virology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China[6]Chengdu Kanghong Pharmaceutical Co., Ltd., Chengdu 610200, Sichuan Province, China
Many advanced cancers are characterized by metabolic disorders. A dietary therapeutic strategy was proposed to inhibit tumor growth through administration of low-carbohydrate, average-protein, and high-fat diet, which is also known as ketogenic diet (KD). In vivo antitumor efficacy of KD on transplanted CT26+ tumor cells in BALB/c mice was investigated. The results showed that the KD group had significantly higher blood β-hydroxybutyrate and lower blood glucose levels when compared with the normal diet group. Meanwhile, KD increased intratumor oxidative stress, and TUNEL staining showed KD-induced apoptosis against tumor cells. Interestingly, the distribution of CD16/32+ and iNOS+ M1 tumor-associated macrophages (TAMs) increased in the KD-treated group, with concomitantly less arginase-1+ M2 TAMs. Moreover, KD treatment downregulated the protein expression of matrix metalloproteinase-9 in CT26+ tumor-bearing mice. Western blot analysis demonstrated that the expression levels of HDAC3/PKM2/NF-κB 65/p-Stat3 proteins were reduced in the KD-treated group. Taken together, our results indicated that KD can prevent the progression of colon tumor via inducing intratumor oxidative stress, inhibiting the expression of the MMP-9, and enhancing M2 to M1 TAM polarization. A novel potential mechanism was identified that KD can prevent the progression of colon cancer by regulating the expression of HDAC3/PKM2/NF-κB65/p-Stat3 axis.
基金：
This work was supported by the Open Project of Shandong Collaborative Innovation Center for Antibody Drugs (nos. CICAD1829 and CIC-AD1834), the Doctoral Foundation of Liaocheng University (nos. 318051738 and 318051827), and the Foundation of Liaocheng University (no. 318011907).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2020]版：
大类|1 区农林科学
小类|1 区农业综合1 区应用化学2 区食品科技
最新[2023]版：
大类|1 区农林科学
小类|1 区农业综合2 区应用化学2 区食品科技
第一作者：
第一作者机构：[1]Institute of Biopharmaceutical Research, Liaocheng University, Liaocheng 252059, China
通讯作者：
推荐引用方式(GB/T 7714)：
Ning Zhang,Chunhong Liu,Li Jin,et al.Ketogenic Diet Elicits Antitumor Properties through Inducing Oxidative Stress, Inhibiting MMP-9 Expression, and Rebalancing M1/M2 Tumor-Associated Macrophage Phenotype in a Mouse Model of Colon Cancer.[J].Journal of agricultural and food chemistry.2020,68(40):11182-11196.doi:10.1021/acs.jafc.0c04041.
APA：
Ning Zhang,Chunhong Liu,Li Jin,Ting Wang,Fang Yang...&Jingchao Chen.(2020).Ketogenic Diet Elicits Antitumor Properties through Inducing Oxidative Stress, Inhibiting MMP-9 Expression, and Rebalancing M1/M2 Tumor-Associated Macrophage Phenotype in a Mouse Model of Colon Cancer..Journal of agricultural and food chemistry,68,(40)
MLA：
Ning Zhang,et al."Ketogenic Diet Elicits Antitumor Properties through Inducing Oxidative Stress, Inhibiting MMP-9 Expression, and Rebalancing M1/M2 Tumor-Associated Macrophage Phenotype in a Mouse Model of Colon Cancer.".Journal of agricultural and food chemistry 68..40(2020):11182-11196
农林科学