Abstract C093: Unlocking the potential of Metformin: Revealing its impact on colorectal cancer cells at a molecular level

Abstract

Abstract Metformin is a drug commonly used to treat type-2 diabetes, but recent studies suggest that it may also have anti-cancer effects by influencing cell cycle arrest and apoptosis. While previous studies have focused on metformin's effect on mTor, the downstream genetic pathways underlying its anti-proliferation mechanism remain unclear. Identifying these pathways may help predict patient response and allow for tailored treatment plans. This study aims to investigate the early genetic pathways involved in colon cancer using an in-vitro cell model and assess the impact of metformin on cell cycle and cancer proliferation in colon cancer cells, taking into account the p53/p21 status. Four different metformin concentrations were used on the HCT116 colon cancer cell line and its genetic modified forms. To determine cell viability and to measure cell cycle and apoptosis, MTT assay and flow cytometer were used. RNA-seq was performed on HCT116 after 24 hours of metformin treatment and pathway analysis was conducted using the Pathway Studio software. Results showed a significant decline in cell viability in response to metformin treatment, with an increase in the apoptosis phase. Transcriptomic analysis revealed that over 3,000 genes were significantly down-regulated, while 1,200 genes were up-regulated. Metformin promotes cell death and fragmentation at the SubG0 level, particularly in the case of p21 null, but p53 likely plays a primary role in driving apoptosis in colorectal cancer cells. In conclusion, metformin has potential in inhibiting proliferation and inducing apoptosis in colorectal cancer cells, affecting molecular pathways involved in the disease. However, further investigation through next-generation sequencing and molecular targeting is necessary to fully understand the disease at different levels. Citation Format: Jamila Hijazi, Pierre Khoueiry, Assaad Eid, Nadine Darwiche, Georges Nemer. Unlocking the potential of Metformin: Revealing its impact on colorectal cancer cells at a molecular level [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C093.