دورية أكاديمية
Downregulation of MDR 1 gene contributes to tyrosine kinase inhibitor induce apoptosis and reduction in tumor metastasis: A gravity to space investigation.
| العنوان: | Downregulation of MDR 1 gene contributes to tyrosine kinase inhibitor induce apoptosis and reduction in tumor metastasis: A gravity to space investigation. |
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| المؤلفون: | Tariq I; Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch- Str. 4, 35037 Marburg, Germany; Punjab University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, 54000 Lahore, Pakistan., Ali MY; Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch- Str. 4, 35037 Marburg, Germany; Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, GC University Faisalabad, Faisalabad, Pakistan., Janga H; Institute for Lung Research, Universities of Giessen and Marburg Lung Center, Philipps University Marburg, German Center for Lung Research (DZL), Hans-Meerwein-Str. 2, 35032 Marburg, Germany., Ali S; Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch- Str. 4, 35037 Marburg, Germany., Amin MU; Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch- Str. 4, 35037 Marburg, Germany., Ambreen G; Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch- Str. 4, 35037 Marburg, Germany., Ali U; Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch- Str. 4, 35037 Marburg, Germany., Pinnapireddy SR; Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch- Str. 4, 35037 Marburg, Germany; CSL Behring GmbH, Emil-von-Behring-Str. 76, 35041 Marburg, Germany., Schäfer J; Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch- Str. 4, 35037 Marburg, Germany., Schulte LN; Institute for Lung Research, Universities of Giessen and Marburg Lung Center, Philipps University Marburg, German Center for Lung Research (DZL), Hans-Meerwein-Str. 2, 35032 Marburg, Germany., Bakowsky U; Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch- Str. 4, 35037 Marburg, Germany. Electronic address: ubakowsky@aol.com. |
| المصدر: | International journal of pharmaceutics [Int J Pharm] 2020 Dec 15; Vol. 591, pp. 119993. Date of Electronic Publication: 2020 Oct 18. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 7804127 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-3476 (Electronic) Linking ISSN: 03785173 NLM ISO Abbreviation: Int J Pharm Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press. |
| مواضيع طبية MeSH: | Apoptosis* , Drug Resistance, Neoplasm*, Caco-2 Cells ; Cell Line, Tumor ; Down-Regulation ; Humans ; Protein Kinase Inhibitors ; RNA, Small Interfering |
| مستخلص: | P-glycoprotein (P-gp) associated multidrug resistance (MDR) represents a major failure in cancer treatment. The overexpression of P-gp is responsible for ATP-dependent efflux of drugs that decrease their intracellular accumulation. An effective downregulation of MDR1 gene using small interfering RNA (siRNA) is one of the safe and effective tools to overcome the P-gp triggered MDR. Therefore, the development of an efficient and non-toxic carrier system for siRNA delivery is a fundamental challenge for effective cancer treatment. Polyamidoamine (PAMAM) dendrimer has been used for efficient delivery of siRNA (dendriplexes) to the tumor cells but the associated toxicity problems render its use in biological applications. A non-covalent lipid modification (lipodendriplexes) is supposed to offer a promising strategy to overcome the demerits linked to the naked dendriplexes system. In the current study, we deliver siRNA, designed against MDR1 gene (si-MDR1), in colorectal carcinoma cells (Caco-2), having overexpression of P-gp, to check the role of MDR1 gene in tumor progression and multidrug resistance using two dimensional (2D) and three dimensional (3D) environment. Imatinib mesylate (IM), a P-gp substrate, was used as model drug. Our results revealed that the effective knockdown by lipodendriplexes system can significantly reduce the tumor cell migration in 2D (p < 0.001) and 3D (p < 0.001) cell cultures as compared to unmodified dendriplexes and si-Control groups. It was also observed that lipodendriplexes aided downregulation of MDR1 gene effectively, re-sensitized the Caco-2 cells for IM uptake and showed a significantly (p < 0.001) higher apoptosis. Our findings imply that our lipodendriplexes system has a great potential for siRNA delivery, however, further in vivo application using a suitable targeted system can play a major role for better cancer therapeutics. (Copyright © 2020. Published by Elsevier B.V.) |
| فهرسة مساهمة: | Keywords: 3D bioprinting; Apoptosis; Gene silencing; Imatinib mesylate; MDR; P-gp; PAMAM; Spheroids |
| المشرفين على المادة: | 0 (Protein Kinase Inhibitors) 0 (RNA, Small Interfering) |
| تواريخ الأحداث: | Date Created: 20201021 Date Completed: 20210617 Latest Revision: 20210617 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1016/j.ijpharm.2020.119993 |
| PMID: | 33086089 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1873-3476 |
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| DOI: | 10.1016/j.ijpharm.2020.119993 |