Picropodophyllin, an IGF‑1 receptor inhibitor, enhances oxaliplatin efficacy in chemoresistant colorectal cancer HCT116 cells by reducing metastatic potential.
Nurcin Kayacik, Hasan Kurter, Tolga Sever, Yasemin Basbinar, Gizem Calibasi-Kocal
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引用次数: 0
Abstract
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 and epithelial-mesenchymal transition (EMT). Targeting the IGF-1R pathway is therefore a promising strategy, not only for overcoming drug resistance, but also for reducing migration and metastatic behavior related to EMT. The present study aimed to evaluate the potential of picropodophyllin (PPP), a selective IGF-1R inhibitor, to enhance the effects of oxaliplatin (OX) in HCT116 and OX-resistant HCT116-R cells. Cell viability was evaluated using a resazurin-based assay following 48-h combination treatment with OX at its IC50 concentrations (HCT116 cells, 53 µM and HCT116-R cells, 324 µM) and PPP (1 µM). Migration was assessed using wound healing assays, with images captured and analyzed at 0 and 48 h. Additionally, immunofluorescence staining was performed to assess E-cadherin and vimentin expression, evaluating epithelial and mesenchymal characteristics. In HCT116-R cells, the combination of OX (53 µM) and PPP significantly reduced cell viability by 0.65-fold compared with OX alone (P=0.0286). Wound healing assays demonstrated that combining PPP with OX (53 and 324 µM) significantly decreased migration, with 0.34-fold and 0.22-fold reductions, respectively (P<0.05). Immunofluorescence staining revealed that this combination also significantly increased E-cadherin expression, by 1.37- and 1.63-fold, respectively (P<0.05), indicating the role of PPP in enhancing epithelial characteristics and reducing EMT-related drug resistance. These findings highlight the potential for combining PPP with OX to enhance the cytotoxic and anti-metastatic effects of OX in chemo-resistant CRC cells, thus offering a promising strategy for overcoming drug resistance and improving patient outcomes in CRC treatment.
期刊介绍：
Oncology Letters is a monthly, peer-reviewed journal, available in print and online, that focuses on all aspects of clinical oncology, as well as in vitro and in vivo experimental model systems relevant to the mechanisms of disease.
The principal aim of Oncology Letters is to provide the prompt publication of original studies of high quality that pertain to clinical oncology, chemotherapy, oncogenes, carcinogenesis, metastasis, epidemiology and viral oncology in the form of original research, reviews and case reports.
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