Anti-metastatic effect of midazolam on melanoma B16F10 cells in the lungs of diabetic mice.

In this study, we investigated the effects of midazolam on inhibiting metastases in the lungs of diabetic mice and on human pulmonary microvascular endothelial cells (HPMVECs). Subcutaneous injection of midazolam inhibited hyperglycemia-induced cancer metastasis in the lungs of diabetic mice. Midazolam also prevented the generation of ROS, activation of TGase, and subsequent vascular leakage in the lungs of diabetic mice. Furthermore, in vitro studies with HPMVECs confirmed that midazolam inhibited VEGF-induced intracellular events including ROS generation, TGase activation, and disruption of vascular endothelial-cadherins, thus preventing the permeability of endothelial cells. Notably, midazolam had no direct effect on the migration or proliferation of melanoma cells, instead acting upon endothelial cells. The midazolam-mediated inhibition of VEGF-induced intracellular events was reversed by treatment with the GABAA receptor antagonist flumazenil. These findings suggest that midazolam prevents hyperglycemia-induced cancer metastasis by inhibiting VEGF-induced intracellular events and subsequent vascular leakage via the GABAA receptors in the lungs of diabetic mice. PMID: 32446885 [PubMed - as supplied by publisher]
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research