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Figure 6 | Experimental Hematology & Oncology

Figure 6

From: ABC transporter activity linked to radiation resistance and molecular subtype in pediatric medulloblastoma

Figure 6

Functional screening experiments show verapamil increases the sensitivity of Daoy medulloblastoma cells to radiation, and stunts population expansion. (A) Investigation of inhibitors of ABC transport (and controls) and their effect on radiation response (dose = 5 Gy), using resazurin based cell viability assay. Racemic verapamil sensitized Daoy cells to radiation, as did both component isomers when used individually. “E” indicates drug carrier = ethanol, “D” indicates carrier = DMSO. Survival score was obtained by dividing mean fluorescence after drug exposure and irradiation by that of wells experiencing the drug without irradiation. Error bars +/− 1 SD. “***” indicates p-value < 0.001 when treatments are compared with carrier control. (B) Mean resazurin fluorescence readings for non-irradiated wells of selected treatments in Panel A, showing verapamil isomers lead to fewer live cells at the end of the 5 day assay period, while the calcium channel inhibitor diltiazem has no effect. Error bars +/− 1 SD. (C) Summary of current state of knowledge regarding the relative biological potencies of S- and R-verapamil. (D) R-verapamil is also a radiation sensitizer of Daoy cells in the clonogenic colony formation assay (dose = 5 Gy, 5 flasks per treatment). Error bars +/− 1 SD. (E) Size distribution histogram of colonies derived from non-irradiated control and (F) non-irradiated R-verapamil treated cells from experiment in panel D. Mean diameter for each colony calculated using digital image analysis.

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