Epidermal growth factor potentiates EGFR(Y992/1173)-mediated therapeutic response of triple negative breast cancer cells to cold atmospheric plasma-activated medium

Peiyu Wang; Renwu Zhou; Rusen Zhou; Shuo Feng; Liqian Zhao; Wenshao Li; Jinyong Lin; Aleksandra Rajapakse; Chia-Hwa Lee; Frank B Furnari; Antony W Burgess; Jennifer H Gunter; Gang Liu; Kostya Ken Ostrikov; Derek J Richard; Fiona Simpson; Xiaofeng Dai; Erik W Thompson

doi:10.1016/j.redox.2023.102976

Epidermal growth factor potentiates EGFR(Y992/1173)-mediated therapeutic response of triple negative breast cancer cells to cold atmospheric plasma-activated medium

Redox Biol. 2024 Feb:69:102976. doi: 10.1016/j.redox.2023.102976. Epub 2023 Nov 29.

Authors

Peiyu Wang¹, Renwu Zhou², Rusen Zhou³, Shuo Feng⁴, Liqian Zhao⁵, Wenshao Li³, Jinyong Lin⁶, Aleksandra Rajapakse⁷, Chia-Hwa Lee⁷, Frank B Furnari⁸, Antony W Burgess⁹, Jennifer H Gunter⁷, Gang Liu⁶, Kostya Ken Ostrikov³, Derek J Richard¹⁰, Fiona Simpson¹¹, Xiaofeng Dai¹², Erik W Thompson⁷

Affiliations

¹ National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China; Centre for Genomics and Personalised Health, School of Biomedical Science, Faculty of Health, Queensland University of Technology, Brisbane, Queensland 4059, Australia; Translational Research Institute, Woolloongabba, Queensland 4102, Australia; State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, PR China.
² State Key Laboratory of Electrical Insulation and Power Equipment, Centre for Plasma Biomedicine, School of Electrical Engineering, Xi'an Jiaotong University, Xi'an 710049, PR China.
³ School of Chemistry and Physics, Queensland University of Technology, Brisbane, Queensland 4000, Australia.
⁴ Department of Dermatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China.
⁵ Department of Neurosurgery, Institute of Brain Disease, Nanfang Hospital of Southern Medical University, Guangzhou 510515, PR China.
⁶ State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, PR China.
⁷ Centre for Genomics and Personalised Health, School of Biomedical Science, Faculty of Health, Queensland University of Technology, Brisbane, Queensland 4059, Australia; Translational Research Institute, Woolloongabba, Queensland 4102, Australia.
⁸ Department of Medicine, University of California San Diego, California 92093, USA.
⁹ Walter and Elisa Hall Institute, Melbourne, Victoria 3052, Australia.
¹⁰ Centre for Genomics and Personalised Health, School of Biomedical Science, Faculty of Health, Queensland University of Technology, Brisbane, Queensland 4059, Australia; Translational Research Institute, Woolloongabba, Queensland 4102, Australia; Cancer and Ageing Research Program, Woolloongabba, Queensland 4102, Australia.
¹¹ Frazer Institute, The University of Queensland, Brisbane, Queensland 4102, Australia.
¹² National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China; Department of Dermatology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China. Electronic address: xiaofengteam@163.com.

Abstract

Cold atmospheric plasma (CAP) holds promise as a cancer-specific treatment that selectively kills various types of malignant cells. We used CAP-activated media (PAM) to utilize a range of the generated short- and long-lived reactive species. Specific antibodies, small molecule inhibitors and CRISPR/Cas9 gene-editing approaches showed an essential role for receptor tyrosine kinases, especially epidermal growth factor (EGF) receptor, in mediating triple negative breast cancer (TNBC) cell responses to PAM. EGF also dramatically enhanced the sensitivity and specificity of PAM against TNBC cells. Site-specific phospho-EGFR analysis, signal transduction inhibitors and reconstitution of EGFR-depleted cells with EGFR-mutants confirmed the role of phospho-tyrosines 992/1173 and phospholipase C gamma signaling in up-regulating levels of reactive oxygen species above the apoptotic threshold. EGF-triggered EGFR activation enhanced the sensitivity and selectivity of PAM effects on TNBC cells. The proposed approach based on the synergy of CAP and EGFR-targeted therapy may provide new opportunities to improve the clinical management of TNBC.

Keywords: Apoptosis; Cold atmospheric plasma; Epithelial growth factor receptor; Triple negative breast cancer.

MeSH terms

Cell Line, Tumor
Epidermal Growth Factor* / metabolism
Epidermal Growth Factor* / pharmacology
ErbB Receptors / metabolism
Humans
Signal Transduction
Triple Negative Breast Neoplasms* / metabolism

Substances

Epidermal Growth Factor
ErbB Receptors
EGFR protein, human