Picropodophyllin, an IGF‑1 receptor inhibitor, enhances oxaliplatin efficacy in chemoresistant colorectal cancer HCT116 cells by reducing metastatic potential

• DOI: 10.3892/ol.2025.14966
• Publication Date: 2025-03-06T07:54:56Z
• Authors: Nurcin Kayacik; Hasan Kurter; Tolga Sever; Yasemin Basbinar; Gizem Calibasi‑Kocal

The insulin‑like growth factor receptor (IGF‑1R) axis drives cellular growth, survival and chemoresistance in colorectal cancer (CRC) by promoting proliferative signaling, anti‑apoptotic effects epithelial‑mesenchymal transition (EMT). Targeting the IGF‑1R pathway is therefore a promising strategy, not only for overcoming drug resistance, but also reducing migration metastatic behavior related to EMT. present study aimed evaluate potential of picropodophyllin (PPP), selective inhibitor, enhance oxaliplatin (OX) HCT116 OX‑resistant HCT116‑R cells. Cell viability was evaluated using resazurin‑based assay following 48‑h combination treatment with OX at its IC₅₀ concentrations (HCT116 cells, 53 <em>&micro;</em>M 324 <em>&micro;</em>M) PPP (1 <em>&micro;</em>M). Migration assessed wound healing assays, images captured analyzed 0 48 h. Additionally, immunofluorescence staining performed assess E‑cadherin vimentin expression, evaluating epithelial mesenchymal characteristics. In (53 significantly reduced cell 0.65‑fold compared alone (P=0.0286). Wound assays demonstrated that combining decreased migration, 0.34‑fold 0.22‑fold reductions, respectively (P&lt;0.05). Immunofluorescence revealed this increased 1.37‑ 1.63‑fold, (P&lt;0.05), indicating role enhancing characteristics EMT‑related resistance. These findings highlight cytotoxic anti‑metastatic chemo‑resistant CRC thus offering strategy resistance improving patient outcomes treatment.