The endocytic pathway of Pt nanoclusters and their induced apoptosis of A549 and A549/Cis cells through c-Myc/p53 and Bcl-2/caspase-3 signaling pathways - 13/11/21
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Abstract |
In recent years, multifunctional platinum nanoclusters (Pt-NCs) as new Pt-based anti-cancer drugs exhibit a promising therapeutic efficiency for several cancer diseases, especially for human pulmonary carcinoma. However, the endocytosis behaviors (like uptake pathway, etc.) and induced apoptosis mechanism of Pt-NCs for drug-resistant non-small cell lung cancer (NSCLC), are still inconclusive. In this research, we explored the endocytic pathway of Pt-NCs in both typical NSCLC A549 cells and cisplatin-resistant A549/Cis cells through qualitative confocal laser scanning microscope (CLSM) measurement and quantitative flow cytometry (FCM) and inductive coupled plasma-optical emission spectroscopy (ICP-OES) analysis, by the means of introducing the specific inhibitors which impede the classical ways of endocytosis. It was found that Pt-NCs dominatingly entered A549 cells via caveolin-mediated endocytosis as well as A549/Cis cells through micropinocytosis approach. Pt-NCs possessed an excellent inhibitory effect on the cell proliferation, migration and invasion, which the cell activity of A549 cells reduced to 14% and that of A549/Cis cells went down about four fifths. Moreover, Pt-NCs treatment increased caspase-3 protein levels and downregulated the expression of c-Myc and Bcl-2, proving the Pt-NCs-induced apoptosis of NSCLC cells was related to c-Myc/p53 and Bcl-2/caspase-3 signal pathways. These results demonstrate the explicit uptake pathway and apoptotic signaling pathway of Pt-NCs for NSCLC, which provides an in-depth and reasonable theoretical basis for the development of new Pt-NCs-based chemotherapeutics in future clinical practice.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Energy-dependent Pt-NCs enter A549 cells mainly via the caveolin-mediated endocytosis and A549/Cis cells through micropinocytosis, which further induces cells apoptosis by means of c-Myc/p53 and Bcl-2/caspase-3 signaling pathways.
Highlights |
• | The uptake of Pt-NCs in both NSCLC A549 cells and cisplatin-resistant A549/Cis cells is energy-dependent. |
• | Pt-NCs mainly dominatingly enter A549 cells via the caveolin-mediated endocytosis. |
• | The Pt-NCs’ endocytosis of cisplatin-resistant A549/Cis cells by the way of micropinocytosis. |
• | Pt-NCs possess an excellent inhibitory effect on the proliferation, migration, and invasion of NSCLC cells. |
• | Pt-NCs induced the apoptosis of NSCLC cells through the c-Myc/p53 and Bcl-2/caspase-3 signal pathways. |
Keywords : Platinum nanoclusters, Non-small cell lung cancer, Caveolin-mediated endocytosis, Micropinocytosis, Cisplatin-resistant, Apoptosis mechanism
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Vol 144
Article 112360- décembre 2021 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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