Nicotinamide Adenine Dinucleotide Precursor Suppresses Hepatocellular Cancer Progression in Mice

被引:8
作者
Pang, Nengzhi [1 ]
Hu, Qianrong [1 ,2 ]
Zhou, Yujia [1 ]
Xiao, Ying [1 ]
Li, Wenli [1 ,3 ]
Ding, Yijie [1 ]
Chen, Yunan [1 ]
Ye, Mingtong [4 ]
Pei, Lei [1 ]
Li, Qiuyan [1 ]
Gu, Yingying [1 ]
Sun, Yan [1 ]
Fang, Evandro Fei [5 ]
Chen, Mianrong [6 ]
Zhang, Zhenfeng [6 ]
Yang, Lili [1 ]
机构
[1] Sun Yat sen Univ, Sch Publ Hlth, Dept Nutr, Guangdong Prov Key Lab Food Nutr & Hlth, Guangzhou 510080, Peoples R China
[2] Guangzhou Baiyun Dist Maternal & Child Hlth Hosp, Dept Women Hlth Care, Guangzhou 510400, Peoples R China
[3] Guangzhou Huadu Dist Ctr Dis Control & Prevent, Dept Immunizat Programmes, Guangzhou 510080, Peoples R China
[4] Huizhou First Maternal & Child Hlth Care Hosp, Huizhou 516007, Peoples R China
[5] Univ Oslo, Akershus Univ Hosp, Dept Clin Mol Biol, N-1478 Lorenskog, Norway
[6] Guangzhou Med Univ, Radiol Ctr, Translat Med Ctr, Guangzhou Key Lab Res & Dev Nanobiomed Technol Dia, Guangzhou 510260, Peoples R China
基金
中国国家自然科学基金;
关键词
hepatocellular carcinoma (HCC); nicotinamide adenine dinucleotide (NAD); nicotinamide riboside (NR); cancer metastasis; BETA SIGNAL-TRANSDUCTION; TUMOR-GROWTH; PATHWAY; METASTASIS; METABOLISM; RIBOSIDE; CARCINOMA; FIBROSIS; CACHEXIA; COMPLEX;
D O I
10.3390/nu15061447
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
Targeting Nicotinamide adenine dinucleotide (NAD) metabolism has emerged as a promising anti-cancer strategy; we aimed to explore the health benefits of boosting NAD levels with nicotinamide riboside (NR) on hepatocellular carcinoma (HCC). We established three in vivo tumor models, including subcutaneous transplantation tumor model in both Balb/c nude mice (xenograft), C57BL/6J mice (allograft), and hematogenous metastatic neoplasm in nude mice. NR (400 mg/kg bw) was supplied daily in gavage. In-situ tumor growth or noninvasive bioluminescence were measured to evaluate the effect of NR on the HCC process. HepG2 cells were treated with transforming growth factor-beta (TGF-beta) in the absence/presence of NR in vitro. We found that NR supplementation alleviated malignancy-induced weight loss and metastasis to lung in nude mice in both subcutaneous xenograft and hematogenous metastasis models. NR supplementation decreased metastasis to the bone and liver in the hematogenous metastasis model. NR supplementation also significantly decreased the size of allografted tumors and extended the survival time in C57BL/6J mice. In vitro experiments showed that NR intervention inhibited the migration and invasion of HepG2 cells triggered by TGF-beta. In summary, our results supply evidence that boosting NAD levels by supplementing NR alleviates HCC progression and metastasis, which may serve as an effective treatment for the suppression of HCC progression.
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页数:17
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