Ovarian cancer (OC) remains one of the leading causes of cancer-related mortality among women. Targeting the insulin-like growth factor 1 (IGF-1) signaling pathway has emerged as a promising therapeutic strategy. Linsitinib, an IGF-1 receptor (IGF-1R) inhibitor, has shown potential in disrupting this pathway. Additionally, metformin, commonly used in the treatment of type 2 diabetes, has been studied for its anti-cancer properties due to its ability to inhibit metabolic pathways that intersect with IGF-1 signaling, making it a candidate for combination therapy in cancer treatments. This study explores the anti-cancer effects of linsitinib and metformin on OVCAR3 cells by the suppression of the IGF-1 signaling pathway by siRNA-mediated IGF-1 gene silencing. The goal is to evaluate their efficacy as therapeutic agents and to emphasize the critical role of this pathway in OC cell proliferation. Cellular viability was evaluated by resazurin-based assay, and apoptosis was assessed by flux cytometry. The results of this study indicate that the combination of linsitinib and metformin exhibits an antagonistic effect (obtained by SynergyFinder 2.0 Software), reducing their anti-neoplastic efficacy in OC cell lines. Statistical analyses were performed using ordinary one-way or two-way ANOVA, followed by Tukey's or Šídák's multiple comparison tests. While linsitinib shows promise as a therapeutic option for OC, further research is needed to identify agents that could synergize with it to enhance its therapeutic efficacy, like the combination with standard chemotherapy in OC (carboplatin and paclitaxel).
Keywords: IGF-1 signaling pathway; apoptosis; cell viability; linsitinib; metformin; ovarian cancer.