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Effects of voltage-gated K+ channel blockers in gefitinib-resistant H460 non-small cell lung cancer cells.

Won Il Jeon, Pan Dong Ryu, So Yeong Lee

Anticancer Res., 2012 Dec , 32, 5279-84

Voltage-gated K(+) (Kv) channels are known to be associated with the proliferation of several types of cancer cells, including lung adenocarcinoma cells, and certain Kv channel blockers inhibit cancer cell proliferation. In the present study, we investigated the effects of Kv channel blockers in gefitinib-resistant H460 non-small cell lung cancer (NSCLC) cells. Treatment with dendrotoxin-κ (DTX-κ), which is a Kv1.1-specific blocker, reduced H460 cell viability and arrested cells in G(1)/S transition during cell-cycle progression. We administered DTX-κ in a xenograft model using nude mice. The tumor volume was reduced by the injection of DTX-κ into the tumor tissues compared to the control group. These results indicate that DTX-κ has antitumor effects in gefitinib-resistant H460 cells through the pathway governing the G(1)/S transition both in vitro and in vivo. These findings suggest that Kv1.1 could serve as a novel therapeutic target for gefitinib-resistant NSCLC.

http://www.ncbi.nlm.nih.gov/pubmed/23225427