High Expression of G6PD Increases Doxorubicin Resistance in Triple Negative Breast Cancer Cells by Maintaining GSH Level

Luo, Man; Fu, Afu; Wu, Renfei; Wei, Na; Song, Kai; Lim, Sierin; Luo, Kathy Qian

doi:10.7150/ijbs.65555



Theranostics

International Journal of Medical Sciences

Nanotheranostics

Journal of Cancer

Journal of Genomics

Global reach, higher impact

Full Text | PDF

Int J Biol Sci 2022; 18(3):1120-1133. doi:10.7150/ijbs.65555 This issue Cite

Research Paper

High Expression of G6PD Increases Doxorubicin Resistance in Triple Negative Breast Cancer Cells by Maintaining GSH Level

Man Luo^1,2#, Afu Fu^2#, Renfei Wu^3#, Na Wei², Kai Song⁴, Sierin Lim², Kathy Qian Luo^3,5✉

1. Interdisciplinary Graduate School, Nanyang Technological University, Singapore.
2. School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore.
3. Faculty of Health Sciences, University of Macau, Macao SAR, China.
4. Department of Bioengineering, University of California, Los Angeles, CA, USA.
5. Ministry of Education-Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macao SAR, China.
#These authors contributed equally to this manuscript.

Citation:

Luo M, Fu A, Wu R, Wei N, Song K, Lim S, Luo KQ. High Expression of G6PD Increases Doxorubicin Resistance in Triple Negative Breast Cancer Cells by Maintaining GSH Level. Int J Biol Sci 2022; 18(3):1120-1133. doi:10.7150/ijbs.65555. https://www.ijbs.com/v18p1120.htm

Other styles

Abstract

Resistance to doxorubicin (DOX) remains a big challenge to breast cancer treatment especially for triple negative breast cancer (TNBC). Our previous study revealed that the antioxidant system plays an important role in conferring metastasis derived DOX resistance. In this study, we used two-dimensional difference gel electrophoresis (2D-DIGE) proteomics to compare the expression profiles of two generations of TNBC cell lines which have increased metastatic ability in nude mice and exhibited resistance to DOX. Through careful analyses, one antioxidant protein: glucose-6-phosphate dehydrogenase (G6PD) was identified with 3.2-fold higher level in metastatic/DOX-resistant 231-M1 than its parental 231-C3 cells. Analyses of clinical data showed that TNBC patients with higher G6PD levels exhibited lower overall survival than patients with lower G6PD level. Reducing G6PD expression by siRNA or inhibiting its activity with dehydroepiandrosterone (DHEA) significantly increased DOX's cytotoxicity in both cell lines. Importantly, inhibiting G6PD's activity with DHEA dramatically increased the apoptotic rate of 1.25 µM DOX from 2% to 54%. Our results suggest that high level of G6PD can help TNBC to resist DOX-induced oxidative stress. Thus, inhibiting G6PD shall be a good strategy to treat DOX-resistant TNBC.

Keywords: Triple negative breast cancer, Metastasis, Doxorubicin, Drug resistance, Oxidative stress, G6PD

Citation styles

APA

Luo, M., Fu, A., Wu, R., Wei, N., Song, K., Lim, S., Luo, K.Q. (2022). High Expression of G6PD Increases Doxorubicin Resistance in Triple Negative Breast Cancer Cells by Maintaining GSH Level. International Journal of Biological Sciences, 18(3), 1120-1133. https://doi.org/10.7150/ijbs.65555.

ACS

Luo, M.; Fu, A.; Wu, R.; Wei, N.; Song, K.; Lim, S.; Luo, K.Q. High Expression of G6PD Increases Doxorubicin Resistance in Triple Negative Breast Cancer Cells by Maintaining GSH Level. Int. J. Biol. Sci. 2022, 18 (3), 1120-1133. DOI: 10.7150/ijbs.65555.

NLM

CSE

Luo M, Fu A, Wu R, Wei N, Song K, Lim S, Luo KQ. 2022. High Expression of G6PD Increases Doxorubicin Resistance in Triple Negative Breast Cancer Cells by Maintaining GSH Level. Int J Biol Sci. 18(3):1120-1133.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.