4-[6-(4-Isopropoxyphenyl)Pyrazolo[1,5-a]Pyrimidin-3-yl]Quinoline) Suppresses Metastasis Through HIF-1α/MCT-4-Mediated Lactate Excretion in Colorectal Cancer Cells

Abstract

DMH1 (D4-[6-(4-isopropoxyphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline) is a bone morphogenetic protein antagonist. However, the influence of DMH1 on colorectal cancer metastasis remains unknown. Hence, This study aimed to investigate the inhibitory effect of DMH1 on the migration of cancer cells. In vitro incubation with DMH1(1mM) inhibited the high protein level of HIF-1α in CT-26 cells. Transwell assay confirmed that DMH1 suppress CT-26 cells migration via the HIF-1α under hypoxia. The accumulation of lactate in culture medium down-regulated the extracellular pH, then stimulated the migration of CT-26 cells. DMH1 suppressed the migration of CT-26 cells through HIF-1α/MCT-4 signaling pathway mediate the excreation of lactate. The data demonstrated that DMH1 downregulated the high intracellular pH levels via the HIF-1α/MCT-4 signaling pathway to mediate lactate excretion. This study indicated that DMH1 might serve as a potential drug for treating tumor migration by minimizing the intracellular pH via the HIF-1α/MCT-4 signaling pathway.