S-Space College of Veterinary Medicine (수의과대학) Dept. of Veterinary Medicine (수의학과) Theses (Master's Degree_수의학과)
Anti-cancer Effects of Voltage-gated K+ Channel Blockers, Dendrotoxin-κ and Margatoxin, in Gefitinib-resistant H460 Lung Cancer Cell Line
- 수의과대학 수의학과
- Issue Date
- 서울대학교 대학원
- 학위논문 (석사)-- 서울대학교 대학원 : 수의학과, 2014. 2. 이소영.
- Membrane ion channels are well known to be associated with various cellular functions in most types of cells. Especially, voltage-gated K+ (Kv) channels are related to the proliferation of several types of cancer cell lines, including lung adenocarcinoma cell line, and certain Kv channel blockers inhibit cancer cell proliferation. Therefore, Kv channels have received attention due to their possibility as promising targets to develop novel anti-cancer therapy. In the present study, we investigated the effects of Kv channel blockers in gefitinib-resistant H460 lung cancer cell line. 1) The mRNA and protein of both Kv1.1 and Kv1.3 were detected in H460 lung cancer cell line. 2) Treatment of Kv1.1 specific blocker, dendrotoxin-κ (DTX-κ), and Kv1.3 specific blockers, margatoxin (MgTX) and 5-(4-phenoxybutoxy) psoralen (PAP-1), reduced H460 cell viability through not apoptosis but cell cycle arrest in G1/S transition during cell cycle progression. 3) Anticancer effects of Kv channel blockers were also shown in xenograft model using nude mice. Tumor volume was reduced by the regular injection of DTX-κ or MgTX into the tumor tissues compared to the control groups. 4) Furthermore, combination treatment of gefitinib with DTX-κ or MgTX leads to synergistic anticancer effects in H460 cell line. These results indicate DTX-κ and MgTX have anticancer effects in gefitinib-resistant H460 cell line through the pathway governing the G1/S transition both in vitro and in vivo. The relation between cell viability and Kv channels, Kv1.1 and Kv1.3, suggests that these Kv channels would serve as novel therapeutic targets for gefitinib-resistant lung cancer cell lines.