Abstract:

Glutamate levels are significantly higher in colon cancer cells than in normal cells. Increased expression of N-methyl-D-aspartate (NMDA) receptors has been observed in tumor cell lines that cause angiogenesis. Vascular endothelial growth factor (VEGF) promotes proliferation and endothelial migration through the calcium influx. As a result, NMDA receptors may be a therapeutic target of cancer, and inhibition of these receptors may reduce tumor growth. In this study, the effects of memantine, an NMDA receptor antagonist, on histology, tumor size, and number, as well as VEGF level in 1,2 dimethylhydrazine (DMH)-induced colon cancer in rats were investigated. Thirty male Wistar rats were divided into three groups: the control group, the colon cancer group (30 mg/kg of DMH solution was injected subcutaneously twice a week for 24 weeks), and the memantine group (20 mg/kg). The results showed that the injection of DMH induced colon polyps (P<0.001) in the colon cancer group, but memantine 20 mg/kg showed protective effects and reduced the number and size of colon polyps (P<0.001). The level of VEGF also increased significantly (P<0.05) in the colon cancer group compared to the control group. Treatment with memantine 20 mg/kg/day reduced VEGF level significantly (P<0.01) in comparison to that of the colon cancer group. The present in vivo study, for the first time, showed the anti-cancer effects of memantine in colon cancer, which can be attributed partially to a reduction in VEGF level.

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