Cell Death and Survival Ca2þ-Activated IK Kþ Channel Blockade (original) (raw)

Ca2þ-activated Kþ channels, such as BK and IK channels, have been proposed to fulfill pivotal functions in neoplastic transfor-mation, malignant progression, and brain infiltration of glioblas-toma cells. Here, the ionizing radiation (IR) effect of IK Kþ channel targeting was tested in human glioblastoma cells. IK channels were inhibited pharmacologically by TRAM-34 or genet-ically by knockdown, cells were irradiatedwith 6MVphotons and IK channel activity, Ca2þ signaling, cell cycling, residual double-strand breaks, and clonogenic survival were determined. In addi-tion, the radiosensitizing effect of TRAM-34was analyzed in vivo in ectopic tumors. Moreover, The Cancer Genome Atlas (TCGA)was queried to expose the dependence of IK mRNA abundance on overall survival (OS) of patients with glioma. Results indicate that radiation increased the activity of IK channels, modified Ca2þ signaling, and induced a G2–M cell-cycle arrest. TRAM-34 decreased the IR-induced accumulation in G2–M arrest...

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