ArticleMedeniyet medical journal2026
Overcoming Regorafenib Resistance in Colorectal Cancer: Synergistic Efficacy of Cilengitide in HT29 and WiDr Cells.
Article in Medeniyet medical journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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3 authors.
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Abstract
Objective: Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide. Regorafenib, a multikinase inhibitor, is approved for the treatment of metastatic CRC; however, the emergence of drug resistance significantly limits its clinical efficacy. Integrins play a key role in tumor progression and therapy resistance, making them attractive therapeutic targets. Methods: Regorafenib-resistant variants of HT29 and WiDr CRC cells were established by long-term exposure to regorafenib. The cytotoxic effects of regorafenib, cilengitide (an αvβ3 and αvβ5 integrin antagonist), and their combination were assessed using MTT assays and clonogenic survival assays. Drug interactions were further evaluated using Chou-Talalay combination index analysis. Results: Resistant cells (HT29-R, WiDr-R) demonstrated markedly elevated IC50 values for regorafenib compared with their parental counterparts. Cilengitide monotherapy reduced clonogenic survival in both parental and resistant lines. Combination treatment with regorafenib and cilengitide showed synergistic inhibition of cell survival (Combination Index <1),particularly in resistant cell lines, suggesting that integrin targeting may restore regorafenib sensitivity. Conclusions: These findings indicate that cilengitide-mediated integrin blockade can overcome resistance to regorafenib in CRC cells, highlighting the therapeutic potential of combining integrin inhibitors with regorafenib in drug-resistant CRC.
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