Potential antitumour effect of all-trans retinoic acid on regorafenib-treated human colon cancer cell lines

Introduction: Colorectal cancer (CRC) is a significant contributor to cancer-related mortality worldwide, ranking as the second leading cause of such deaths. Central to the progression of this malignancy is angio-genesis - a complex process orchestrated by vascular endothelial growth factor (VEGF). Regorafenib, a potent multikinase inhibitor, acts as a critical antagonist of multiple kinases involved in angiogenesis, proliferation, and metastasis. Conversely, all-trans retinoic acid (ATRA) has demonstrated compel-ling antitumour effects across various cancer types. This study aims to com-prehensively evaluate the combined antitumour potential of ATRA and regorafenib in human colon cancer cell lines while elucidating the intricate molecular mechanisms that underlie their action.Material and methods: Our investigative approach involved an enzyme-linked immunosorbent assay to meticulously analyse the levels of key players in the VEGF signalling pathway, including VEGF itself, activated protein kinase (AMPK), extracellular signal-regulated protein kinase 1 (ERK1), and nuclear factor kappa B (NF-kappa B). Additionally, we assessed caspase-3 activity as a fundamental marker of apoptosis.Results: The combined use of ATRA and regorafenib exhibited a remarkable augmentation in both AMPK and caspase-3 activities. This was accompanied by a significant reduction in VEGF, ERK1, and NF-kappa B levels within human colon cancer cell lines subjected to regorafenib treatment.Conclusions: Our findings underscore the remarkable antiproliferative, anti-angiogenic, and proapoptotic effects resulting from the combined use of ATRA and regorafenib in the context of CRC. This modulation of tumouri-genic processes is predominantly me-diate d through the VEGF signalling axis.