Glioblastoma is highly invasive and infiltrates the brain, which makes complete removal difficult. The cancer stem cells which resist chemoradiotherapy cause recurrence of glioblastoma. Thus, it is a promising therapy target. Recent studies have shown that Ion channels are involved in cell proliferation, metastasis, and invasion in cancer.
We identified inhibitors of ion channels in cancer stem cells for treatment of recurrent glioblastoma.
Cancer stem cells were established from a surgical specimen of patients of recurrent glioblastoma by sphere culture methods. We measured whole-cell currents of cancer stem cells using patch-clamp techniques, detected the distribution of ion channel proteins using fluorescent immunostaining, and performed WST-8 cell proliferation assay.
Two cancer stem cell lines were established from specimens of recurrent glioblastoma. The cancer stem cells expressed non-selective cation currents. We identified verapamil, an inhibitor of TRPML channels, from thirty compounds. The TRPML1 and TRPML3 proteins were localized in the cell membrane of cancer stem cells. Verapamil suppressed the cell proliferation of cancer.
The results indicate that verapamil may be a novel drug for recurrent glioblastoma.

To: 要旨(抄録)