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浙江大学学报（医学版）
J Zhejiang Univ (Med Sci)  2019, Vol. 48 Issue (3): 296-302    DOI: 10.3785/j.issn.1008-9292.2019.06.10
    
High dose vitamin C inhibits proliferation of breast cancer cells through reducing glycolysis and protein synthesis
WANG Qingmei(),XU Qianzi,WEI Anyi,CHEN Shishuo,ZHANG Chong*(),ZENG Linghui*()
School of Medicine, Zhejiang University City College, Hangzhou 310015, China
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Abstract  

Objective: To investigate the effects of high dose vitamin C (VC) on proliferation of breast cancer cells and to explore its mechanisms. Methods: Human breast cancer cells Bcap37 and MDA-MB-453 were treated with VC at low dose (0.01 mmol/L), medium dose (0.10 mmol/L) and high dose (2.00 mmol/L). Cell proliferation was determined with CCK-8 assay, protein expression was evaluated by Western blot, and the secretion of lactic acid in tumor cells was detected by colorimetric method. Bcap37 cells were inoculated in nude mice, and tumor baring nude mice were intraperitoneally injected with high VC(4 g/kg, VC group, n=5)or normal saline (control group, n=5) for 24 d. Tumor weight and body weight were calculated. Results: In vitro experiments demonstrated that high dose VC significantly inhibited cell proliferation in Bcap37 and MDA-MB-453 cells (all P < 0.01); the expressions of Glut1 and mTOR signaling pathway-related proteins were decreased (all P < 0.05); and the secretion of lactic acid was also markedly reduced (all P < 0.05). In vivo experiment showed that the tumor weight was decreased in mice treated with high-dose VC as compared with control group (P < 0.05), but no difference in body weights between two groups was observed. Conclusion: High dose VC may inhibit proliferation of breast cancer cells both in vitro and in vivo through reducing glycolysis and protein synthesis.

Key words： Breast neoplasms/physiopathology      Ascorbic acid/administration &      dosage      Glucose transporter type 1/metabolism      Protein-serine-threonine kinases/biosynthesis      Signal transduction      Lactic acid/metabolism      Cell proliferation     
Received: 30 January 2019      Published: 04 September 2019
CLC:  R73-3  
  R737.9  
Corresponding Authors: ZHANG Chong,ZENG Linghui     E-mail: 2747912115@qq.com;zhangchong@zucc.edu.cn;zenglh@zucc.edu.cn
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WANG Qingmei
XU Qianzi
WEI Anyi
CHEN Shishuo
ZHANG Chong
ZENG Linghui
Cite this article:

WANG Qingmei, XU Qianzi, WEI Anyi, CHEN Shishuo, ZHANG Chong, ZENG Linghui. High dose vitamin C inhibits proliferation of breast cancer cells through reducing glycolysis and protein synthesis. J Zhejiang Univ (Med Sci), 2019, 48(3): 296-302.

URL:

http://www.zjujournals.com/med/10.3785/j.issn.1008-9292.2019.06.10     OR     http://www.zjujournals.com/med/Y2019/V48/I3/296


大剂量维生素C通过减少糖酵解和蛋白质合成抑制乳腺癌细胞增殖

目的: 观察大剂量维生素C对乳腺癌细胞增殖及荷瘤小鼠肿瘤生长的影响，并探索其中的机制。方法: 以乳腺癌细胞Bcap37和MDA-MB-453为体外研究对象，分别给予小（0.01 mmol/L）、中（0.10 mmol/L）、大（2.00 mmol/L）剂量的维生素C。采用CCK-8试剂盒检测细胞增殖；蛋白质印迹法检测葡萄糖转运蛋白1（Glut1）和哺乳动物雷帕霉素靶蛋白（mTOR）信号通路相关蛋白表达；乳酸脱氢酶比色法测定乳酸含量。同时，取10只6周龄雌性BALB/c裸鼠，采用皮下接种乳腺癌Bcap37细胞建立荷瘤小鼠移植瘤模型，取5只小鼠腹腔注射维生素C（4 g/kg），观察肿瘤重量和小鼠体质量的变化。结果: 体外细胞学实验结果显示，与空白对照组比较，大剂量维生素C作用下Bcap37和MDA-MB-453细胞增殖受到抑制（均P < 0.01），Glut1转运蛋白表达减少（均P < 0.05），乳酸分泌量减少（均P < 0.01），mTOR信号通路相关蛋白表达水平下调（均P < 0.05）。体内实验结果显示，与对照组比较，大剂量维生素C组肿瘤重量明显减小（P < 0.05），但体质量增长无明显变化。结论: 大剂量维生素C可抑制乳腺癌细胞增殖，这一效果可能与大剂量维生素C抑制乳腺癌细胞能量摄取和下调mTOR信号通路有关。


关键词： 乳腺肿瘤/病理生理学,  抗坏血酸/投药和剂量,  葡萄糖转运体1型/代谢,  蛋白质丝氨酸苏氨酸激酶/生物合成,  信号传导,  乳酸/代谢,  细胞增殖 
Fig 1 Effects of different doses of vitamin C on proliferation of breast cancer cells
Fig 2 Effects of different doses of vitamin C on Glut1 and PFKP expression in breast cancer cells
Fig 3 Effects of different doses of vitamin C on secretion of lactic acid in breast cancer cells
Fig 4 Effects of different doses of vitamin C on mTOR signaling pathway in breast cancer cells
Fig 5 Tumor tissues of the control and experimental group received high dose of vitamin C
Fig 6 Weight growth of the control and experimental group received high dose of vitamin C
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