Combination effects of ellagic acid with erlotinib in a Ba/F3 cell line expressing EGFR H773_V774 insH mutation.
Thorac Cancer. 2020 08 ;11(8):2101-2111. Epub 2020 Jun 11. PMID: 32525282
BACKGROUND: Epidermal growth factor receptor H773_V774 insH (EGFR-insH) is an EGFR exon 20 insertion mutation in non-small cell lung cancer (NSCLC), which is naturally resistant to available EGFR tyrosine kinase inhibitors (TKIs) and lacks a patient-derived cell line.
METHODS: A Ba/F3 cell line expressing EGFR-insH mutation (Ba/F3-insH cell line) was generated using an IL3-deprivation method. A cell proliferation assay was performed to screen natural compounds that exhibit a synergistic effect with erlotinib. Trypan blue staining was used to assess cell growth and crystal violate staining was recruited to evaluate clonogenic potential. Flow cytometry was used to detect EGFR expression and cell apoptosis. A xenograft model was created to evaluate the effect of ellagic acid (EA) with erlotinib on tumor growth.
RESULTS: EA was identified to synergistically inhibit the proliferation of Ba/F3-insH cells with erlotinib. The growth and clonogenic potential of Ba/F3-insH cells were definitely constrained by EA with erlotinib, whereas, the apoptosis of Ba/F3-insH cells was dramatically promoted by the combination. In a xenograft model of the Ba/F3-insH cell line, the combination treatment also exhibited a synergistic reduction in tumor growth.
CONCLUSIONS: In this study, we generated a Ba/F3 cell line expressing EGFR H773_V774 insH mutation and identified a synergistic treatment (EA with erlotinib) that markedly inhibited the viability of Ba/F3-insH cells in vitro and in vivo.
KEY POINTS: Our results indicated that the combination of ellagic acid with erlotinib has synergistic effects against EGFR H773_V774 insH mutation.