Dopamine induces growth inhibition and vascular normalization through reprograming M2-polarized macrophages in rat C6 glioma.

Dopamine induces growth inhibition and vascular normalization through reprograming M2-polarized macrophages in rat C6 glioma.
Toxicol Appl Pharmacol. 2015 Mar 25;
Authors: Qin T, Wang C, Chen X, Duan C, Zhang X, Zhang J, Chai H, Tang T, Chen H, Yue J, Li Y, Yang J
Abstract
Dopamine (DA), a monoamine catecholamine neurotransmitter with antiangiogenic activity, stabilizes tumor vessels in colon, prostate and ovarian cancer, thus increases chemotherapeutic efficacy. Here, in the rat C6 glioma models, we investigated the vascular normalization effects of DA and its mechanisms of action. DA (25, 50 mg/kg) inhibited tumor growth, while a precursor of DA (levodopa) prolonged the survival time of rats bearing orthotopic C6 glioma. DA improved tumor perfusion, with significant effects from day 3, and a higher level at day 5 to 7. In addition, DA decreased microvessel density and hypoxia-inducible factor-1α expression in tumor tissues, while increasing the coverage of pericyte. Conversely, an antagonist of dopamine receptor 2 (DR2) (eticlopride) but not DR1 (butaclamol) abrogated DA-induced tumor regression and vascular normalization. Furthermore, DA improved the delivery and efficacy of temozolomide therapy. Importantly, DA increased representative M1 markers (iNOS, CXCL9, etc.), while decreasing M2 markers (CD206, arginase-1, etc.). Depletion of macrophages by clodronate or zoledronic acid attenuated the effects of DA. Notably, DA treatment...

Source: Toxicology and Applied Pharmacology - March 25, 2015 Category: Toxicology Authors: Qin T, Wang C, Chen X, Duan C, Zhang X, Zhang J, Chai H, Tang T, Chen H, Yue J, Li Y, Yang J Tags: Toxicol Appl Pharmacol Source Type: research