Investigation of the synergistic effect of metformin and FX11 on PANC-1 cell lines.

Abstract

Background: Pancreatic cancer is among the most aggressive and malignant tumors and is a leading cause of cancer-related mortality. It is characterized by its metabolic Warburg effect and glucose dependence. Aerobic glycolysis is a key feature of metabolic reprogramming in cancer cells. This study investigates the combined effect of metformin and FX11, hypothesizing that disrupting cancer cell energetics through complementary mechanisms may result in a synergistic therapeutic effect. The combination of metformin and FX11 affects the axis that regulates vital functions in cancer cells; thus, the uncontrolled growth of tumor cells, especially those that use a lactose-dependent energy pathway, can be controlled. Several in vitro experiments were conducted to evaluate this hypothesis. PANC-1 cell proliferation was assessed using an MTS assay, lactate levels were measured via an LDH assay, and apoptosis was determined using a flow cytometry-based PE-annexin V assay. The downstream effects of metformin and FX11 treatment were evaluated via western blot analysis.

Results: The findings of this study revealed that metformin and FX11 significantly decreased the viability of PANC-1 cells when used in combination, and this effect was achieved by significantly affecting the energy mechanism of the cells through the AMPKα axis. Furthermore, the lactate levels in PANC1 cells co-treated with metformin and FX11 were significantly decreased, while the increased cellular stress led the cells to apoptosis.

Conclusions: Compared with metformin treatment alone, the combination treatment of metformin and FX11 stimulates cellular stress in pancreatic cancer and targets various energy processes that encourage cancer cells to undergo apoptosis. This study provides a novel therapeutic strategy for the treatment of pancreatic cancer.