Abstract
Non-small cell lung cancer (NSCLC) is among the leading causes of human mortality due to a lack of effective treatments. Conventional chemotherapies affect healthy cells and cause multidrug resistance, while tumors may eventually develop resistance to less-toxic targeted therapies. Thus, the need to develop novel therapies for NSCLC is urgent. Here, we show that Nile tilapia-derived Tilapia piscidin (TP) 4 is cytotoxic to a panel of NSCLC cells with different genetic profiles. We observed that TP4 triggers NSCLC cell death through the necrosis and combining TP4 with potent Epidermal growth factor receptor (EGFR)- tyrosine kinase inhibitors (TKI)s, Erlotinib, and Gefitinib, improved drug responses in EGFR-mutated NSCLC cells, but not in EGFR-wild-type NSCLC cells. This work provides novel insights into potential NSCLC treatments, which may utilize antimicrobial peptide TP4 as monotherapy or in combination with EGFR-TKIs.
Keywords:
Antimicrobial peptide (AMP), Tilapia piscidin 4 (TP4), non-small cell lung cancer (NSCLC).
MeSH terms
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Animals
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Antimicrobial Cationic Peptides / isolation & purification
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Antimicrobial Cationic Peptides / pharmacology*
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Antimicrobial Cationic Peptides / therapeutic use
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Antineoplastic Combined Chemotherapy Protocols / pharmacology*
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Apoptosis / drug effects
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Carcinoma, Non-Small-Cell Lung / drug therapy*
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Carcinoma, Non-Small-Cell Lung / genetics
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Cell Line, Tumor
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Cichlids*
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Drug Resistance, Multiple / genetics
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Drug Resistance, Neoplasm / drug effects
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Drug Resistance, Neoplasm / genetics
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Drug Screening Assays, Antitumor
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Drug Synergism
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ErbB Receptors / genetics
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Erlotinib Hydrochloride / pharmacology
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Fish Proteins / isolation & purification
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Fish Proteins / pharmacology*
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Fish Proteins / therapeutic use
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Gefitinib / pharmacology
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Humans
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Lung Neoplasms / drug therapy*
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Lung Neoplasms / genetics
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Protein Kinase Inhibitors / pharmacology
Substances
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Antimicrobial Cationic Peptides
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Fish Proteins
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Protein Kinase Inhibitors
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Erlotinib Hydrochloride
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EGFR protein, human
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ErbB Receptors
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Gefitinib