rRGD3, a Triple-RGD Recombinant Peptide, Suppresses Malignant Phenotypes in Nasopharyngeal Carcinoma-Associated Models Through the Modulation of ITGB1-Associated FAK/AKT Signaling.
Source: PubMed, NCBI / U.S. National Library of Medicine
Nasopharyngeal carcinoma-associated malignant epithelial models remain useful for exploring integrin-related therapeutic strategies. In this study, we evaluated the antitumor activity and potential mechanisms of rRGD3, a recombinant peptide with a triple-RGD architecture. Using CNE2 cells as the primary experimental model, we evaluated cell viability, colony formation, migration, invasion, adhesion, apoptosis-related marker expression, and EMT-associated molecular changes. In vivo efficacy was assessed using a CNE2 cell-derived BALB/c nude mouse xenograft model. rRGD3inhibited CNE2 cell viability, clonogenic growth, migration, invasion, and adhesion in a dose-dependent manner and suppressed xenograft tumor growth under the tested dosing schedule. Mechanistically, rRGD3promoted mitochondria-associated apoptosis, as indicated by an increased Bax/Bcl-2 ratio and caspase-9/3 activation, and modulated the expression of EMT-associated markers, including E-cadherin, N-cadherin, vimentin, and MMP2. Bioinformatic analysis and experimental validation suggested that ITGB1-containing integrin complexes might serve as important mediators and putative cellular engagement sites of rRGD3. rRGD3treatment reduced ITGB1 protein abundance and attenuated FAK/AKT signaling. ITGB1 knockdown partially mimicked the effects of rRGD3and reduced the additional cellular response to rRGD3treatment, supporting the substantial contribution of ITGB1-associated signaling. These findings provide preliminary me
Abstract
Nasopharyngeal carcinoma-associated malignant epithelial models remain useful for exploring integrin-related therapeutic strategies. In this study, we evaluated the antitumor activity and potential mechanisms of rRGD3, a recombinant peptide with a triple-RGD architecture. Using CNE2 cells as the primary experimental model, we evaluated cell viability, colony formation, migration, invasion, adhesion, apoptosis-related marker expression, and EMT-associated molecular changes. In vivo efficacy was assessed using a CNE2 cell-derived BALB/c nude mouse xenograft model. rRGD3inhibited CNE2 cell viability, clonogenic growth, migration, invasion, and adhesion in a dose-dependent manner and suppressed xenograft tumor growth under the tested dosing schedule. Mechanistically, rRGD3promoted mitochondria-associated apoptosis, as indicated by an increased Bax/Bcl-2 ratio and caspase-9/3 activation, and modulated the expression of EMT-associated markers, including E-cadherin, N-cadherin, vimentin, and MMP2. Bioinformatic analysis and experimental validation suggested that ITGB1-containing integrin complexes might serve as important mediators and putative cellular engagement sites of rRGD3. rRGD3treatment reduced ITGB1 protein abundance and attenuated FAK/AKT signaling. ITGB1 knockdown partially mimicked the effects of rRGD3and reduced the additional cellular response to rRGD3treatment, supporting the substantial contribution of ITGB1-associated signaling. These findings provide preliminary mechanistic evidence that rRGD3suppresses malignant phenotypes in CNE2-based models, at least in part through modulation of ITGB1-associated FAK/AKT signaling.