Novel Drug DCQ Induces Colon Cancer Cell Apoptosis Through HIF‐1α Pathway

Abstract

Recent developments in the field of cancer genomics have shown transcription factor HIF‐1α as a major player in the survival and proliferation of colorectal tumors. Presence of hypoxic areas in tumors facilitate the differentiation and nuclear translocation of HIF‐1α which leads to transcription of hypoxic genes causing vascularization and metastasis of tumors. Hypoxia targeted drug engineering has led to significant advancements in cancer treatments as a method of directly utilizing the hypoxic regions against the tumor to cause cell death and inhibition of growth. Novel drug DCQ (2‐benzoyl‐3‐phenyl 6,7‐dichloroquinoxaline 1,4‐dioxide) has shown promising anti‐tumor results in‐vitro and in‐vivo. The purpose of this study was to utilize a tumor xenograft mouse model to investigate the effectiveness and mechanism of action of DCQ. Methods: 10 week old Balb/c mice were injected subcutaneously with 2 million CT‐29 cells and were monitored for tumor growth over 14 days. Then, mice were randomly assigned to two treatment groups: DCQ treatment given at 17mg/kg body weight and 100μL DMSO injection as control. Injections were given bi‐weekly over a four week period. At sacrifice, tumors were obtained and sectioned. Results: DCQ caused significant decrease in tumor weight (p<0.05) and final tumor area (p<0.05) at time of sacrifice than DMSO injected mice. Histological analysis showed increased total apoptotic area (p<0.05) in tumor tissue sections. Western blot analysis showed a decreased nuclear expression of HIF‐1α (p<0.05).ConclusionsDCQ increases tumor apoptosis through mechanisms involving down regulation of HIF‐1α. Future investigations will observe the effect of DCQ using APCmin/+ mouse model in a supplemental study.