Blockade of Hypoxia: The Impact on Tumor Growth in an Experimental Tumor Model

Abstract

Background: Tumor microenvironment is an active factor participating in immunoregulation, thereby preventing immunosurveillance and limiting the efficacy of anticancer therapies. Hypoxia as a major characteristic of solid tumors causes the expression of Hypoxia-Inducible Factor-1α (HIF-1α). This is a transcription factor that mediates hypoxic responses of tumor cells and involves in the expression of tumor immunosuppression-related genes. Materials and Methods: In this study, we used a mouse 4T1 breast cancer model.Results: Our obtained data revealed that in vivo administration of PX-478, an inhibitor of oxygen sensitive HIF-1α, reduced the expression of Forkhead box P3 (Foxp3) transcript, a molecule that is directly controlled by HIF-1. The level of vascular endothelial growth factor, another gene controlled by HIF-1, remained unchanged. The observed results were in correlation with delayed tumor growth in tumor-bearing mice.Conclusion: Our findings indicate that the reduction in Foxp3 expression through HIF-1α inhibition using PX-478 may contribute to tumor regression.