Journal
CELL AND BIOSCIENCE
Volume 9, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s13578-019-0322-y
Keywords
Apigenin; EGFR; ABT-263; FoxO3a; Noxa
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Funding
- National Natural Science Foundation of China [81872250]
- Natural Science Foundation of Shaanxi Province, China [2016JM8102]
- Program of Innovative Research Team for the Central Universities [GK201701005]
- Fundamental Research Funds for the Central Universities [GK201701009]
- Student Innovation Training Program, Shaanxi Normal University [201810718056]
- Innovation Fund for graduate students [2017CSY017]
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BackgroundMutated epidermal growth factor receptor (EGFR) is one of the most successful targets in cancer targeted therapy. While this treatment has benefited many patients with an activating EGFR mutation (EGFRm), almost all those who initially benefited will eventually develop acquired drug resistance (ADR) after a certain period of time. New therapeutic strategies need to be explored to treat EGFRm tumors and overcome or minimize this recurring ADR.ResultsOur data showed that apigenin alone has only mild inhibitory effects on EGFRm tumor cells. By drug screening, we found that ABT-263 can significantly enhance the antitumor activities of apigenin in tumor cells harbouring an activating EGFR mutation and AZD9291-resistant H1975 cells. Mechanistically, apigenin upregulated the expression of Noxa in EGFRm tumor cells by targeting the AKT-FoxO3a pathway, thereby synergizing with ABT-263 to suppress tumor cell growth and proliferation in vitro and in vivo.ConclusionsOur study provides a rationale for the clinical application of the combination treatment of apigenin and BH3 mimetics in the treatment of EGFRm tumors.
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