Calcium channel antagonists inhibit growth of subcutaneous xenograft meningiomas in nude mice

Abstract

BACKGROUND We have previously shown that calcium channel antagonists inhibit in vitro meningioma growth. This study examines the effect of calcium channel antagonists on in vivo xenograft meningioma growth. METHODS Meningioma cells taken from human patients were mixed with Matrigel and injected into the subcutaneous space in the flank of nude mice. These animals were treated with calcium channel antagonists in their drinking water. Tumor volumes were measured over time; comparison was made between control and treatment groups. Daily weights, average daily water consumption, and serum calcium channel antagonist levels were determined. Comparison of histology and proliferation index was made between control and treatment groups. RESULTS Diltiazem treatment decreased tumor growth over time compared to control groups. Increased tumor growth inhibition was seen with increasing doses ( p > 0.05). Treatment with verapamil had similar effects; however, there are no statistically significant dose dependent decreases in growth with increasing verapamil doses. There were no tumor “cures” or spontaneous regression of tumor in any group including the control groups. Animal daily weight and average daily water consumption was unaffected by increasing calcium channel antagonist doses compared to control groups. Mouse serum drug levels increased with increasing doses of drug in the drinking water of treatment groups ( p > 0.05). Histology and proliferative index of treatment groups were similar to control groups. CONCLUSION Calcium channel antagonists decrease but do not completely inhibit the growth of meningiomas in nude mice. Clinical correlations and potential applications are discussed.