Investigation of the Mechanism and Effect of Enalapril, Angiotensin-Converting Enzyme (ACE) Inhibitor, on Proliferation, Apoptosis, and Migration in Colorectal Cancer Cells

Colorectal cancer is one of the most common cancers in Iran, and despite high cure rate, it still has high mortality. Some studies have shown that angiotensin-converting enzyme (ACE) inhibitors are effective in treating cancer in addition to treating hypertension. The aim of this study was to investigate the effect of enalapril on the proliferation, migration, and expression of ACE, angiotensin II type I receptor (AT1R), vascular endothelial growth factor-A (VEGF-A), and transforming growth factor beta 1 (TGF-β1) genes in colorectal cancer cells.

In this study, the effect of enalapril on the survival rate of CT26, HT29, and SW480 colorectal cancer cells was determined using MTT assay, cell migration was assayed using migration assay technique, and cell cycle assay was performed using flow cytometry. Expression of matrix metalloproteinase 3 (MMP3), MMP9, and epithelial cadherin (E-cadherin), ACE, AT1R, VEGF-A, and TGF-β1 genes were also evaluated using real-time polymerase chain reaction (PCR) technique and reactive oxygen species in these three cell lines.

Enalapril had anti-proliferative and anti-migrate effect on all three colorectal cancer cell lines compared to the control group. Expression of E-cadherin, MMP3, and MMP9 genes significantly decreased after treatment with enalapril (P < 0.001). Expression of ACE, AT1R, VEGF-A, and TGF-β1 genes showed a significant decrease in the three cell lines, and the level of reactive oxygen species significantly increased in the three cell lines compared to the control group.

Given the various anticancer effects of enalapril, it seems that at least alongside standard chemotherapy drugs, enalapril may be useful in the treatment of colorectal cancer.