Journal
BMC PHARMACOLOGY & TOXICOLOGY
Volume 18, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s40360-017-0118-9
Keywords
Lung cancer cell; Drug resistance; Side population; Voltage-gated potassium channel; Combination therapy
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Funding
- Basic Science Research Program through National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning [2012-R1A2A2A01047151, NRF-2014R1A1A3A04052757]
- Bio & Medical Technology Development Program of the National Research Foundation - Ministry of Science, ICT & Future Planning [2016M3A9B6026771]
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Background: Side-population (SP) cells that exclude anti-cancer drugs have been found in various tumor cell lines. Moreover, SP cells have a higher proliferative potential and drug resistance than main population cells (Non-SP cells). Also, several ion channels are responsible for the drug resistance and proliferation of SP cells in cancer. Methods: To confirm the expression and function of voltage-gated potassium (Kv) channels of SP cells, these cells, as well as highly expressed ATP-binding cassette (ABC) transporters and stemness genes, were isolated from a gefitinib-resistant human lung adenocarcinoma cell line (NCI-H460), using Hoechst 33342 efflux. Results: In the present study, we found that mRNA expression of Kv channels in SP cells was different compared to Non-SP cells, and the resistance of SP cells to gefitinib was weakened with a combination treatment of gefitinib and Kv channel blockers or a Kv7 opener, compared to single-treatment gefitinib, through inhibition of the Ras-Raf signaling pathway. Conclusions: The findings indicate that Kv channels in SP cells could be new targets for reducing the resistance to gefitinib.
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