an inhibitor of k+ channels modulates human endometrial tumor-initiating cells抑制剂的k +通道调节人类子宫内膜肿瘤起源细胞.pdfVIP

Schickling et al. Cancer Cell International 2011, 11:25 /content/11/1/25 PRIMARY RESEARCH Open Access An inhibitor of K+ channels modulates human endometrial tumor-initiating cells 1 2,3 1,4 2,3,4 1* Brandon M Schickling , Nukhet Aykin-Burns , Kimberly K Leslie , Douglas R Spitz and Victoria P Korovkina Abstract + Background: Many potassium ion (K ) channels function as oncogenes to sustain growth of solid tumors, but their role in cancer progression is not well understood. Emerging evidence suggests that the early progenitor cancer cell subpopulation, termed tumor initiating cells (TIC), are critical to cancer progression. Results: A non-selective antagonist of multiple types of K+ channels, tetraethylammonium (TEA), was found to suppress colony formation in endometrial cancer cells via inhibition of putative TIC. The data also indicated that withdrawal of TEA results in a significant enhancement of tumorigenesis. When the TIC-enriched subpopulation was isolated from the endometrial cancer cells, TEA was also found to inhibit growth in vitro. Conclusions: These studies suggest that the activity of potassium channels significantly contributes to the progression of endometrial tumors, and the antagonists of potassium channels are candidate anti-cancer drugs to specifically target tumor initiating cells in endometrial cancer therapy. Keywords: endometrial cancer, potassium channels, cancer stem cells, tumor initiating cells Introduction pharmacologic approaches to prevent TIC-mediated + tumorige