ANP-vessel Dilator Enhances the Effect of Trametinib on Colorectal Cancer Cells via the MAPK Pathway

Abstract

Background Colorectal cancer (CRC) is a common malignant disease that involves the interaction of both genetic and environmental factors. Trametinib (TNB) has been approved alone or in combination with dabrafenib to treat melanoma. Vessel dilator (VDL) is a cardiac hormone that possesses anticancer properties. This study evaluates TNB with VDL combined effects in CRC cells and explores the role of Mutagen-activated protein kinases (MAPK, ERK1/2) in this effect. Methods The HCT-15 CRC cells were treated with TNB and VDL. The MTT and ELISA assays were used to assess p-ERK, VEGF, and VEGFR levels. Results The results showed that combined treatment of TNB with VDL produced a significant and synergistic inhibition of HCT-15 cell growth with a combination index of less than 1. A combination treatment demonstrated no change in the expression of VEGF, inhibition of VEGFR2, and reduction of p-ERK1/2 in HCT-15 cells. Conclusion The findings encourage further evaluation of this combination as the combined effect is not mediated through p-ERK, VEGF, and VEGFR.