J Cancer 2019; 10(3):757-764. doi:10.7150/jca.28087

Research Paper

Oxidized Vitamin C (DHA) Overcomes Resistance to EGFR-targeted Therapy of Lung Cancer through Disturbing Energy Homeostasis

Mingtong Ye3#, Nengzhi Pang1#, Ting Wan4, Yuanling Huang1, Tianyi Wei3, Xuye Jiang1, Yujia Zhou1, Yufeng Huang2, Hainan Yang2, Zhenfeng Zhang2✉, Lili Yang1✉

1. Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-Sen University, Guangzhou, Guangdong, PR China.
2. Department of Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, PR China.
3. The First Women and Children's Hospital of Huizhou, Huizhou, Guangdong, PR China.
4. Huizhou First People's Hospital, Huizhou, Guangdong, PR China.
#These authors contribute equally to this work.


Switching aerobic respiration to anaerobic glycolysis of cancer cells plays an important role in development and progression of acquired resistance. Since vitamin C enabled the inhibition of glycolysis of cancer cells, and erlotinib-resistant sub-line of HCC827 (ER6 cells) switched its metabolic features to higher glycolysis for survival, we hypothesize that vitamin C is able to inhibit glycolysis of ER6 cells. In this study, we found that both reduced vitamin C and oxidized vitamin C (DHA) could selectively suppress the viability of ER6 cells. DHA was efficient in inhibiting glycolysis and leading to energy crisis, which could be one mechanism for overcoming drug resistance to erlotinib of ER6 cells. Our data suggest that applying DHA could be a novel treatment strategy for NSCLC with acquired resistance to targeted therapy.

Keywords: Drug resistance, oxidized vitamin C (DHA), energy homeostasis, glycolysis.

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How to cite this article:
Ye M, Pang N, Wan T, Huang Y, Wei T, Jiang X, Zhou Y, Huang Y, Yang H, Zhang Z, Yang L. Oxidized Vitamin C (DHA) Overcomes Resistance to EGFR-targeted Therapy of Lung Cancer through Disturbing Energy Homeostasis. J Cancer 2019; 10(3):757-764. doi:10.7150/jca.28087. Available from http://www.jcancer.org/v10p0757.htm