Verapamil inhibits tumor progression of chemotherapy-resistant pancreatic cancer side population cells
| العنوان: | Verapamil inhibits tumor progression of chemotherapy-resistant pancreatic cancer side population cells |
|---|---|
| المؤلفون: | Karl-Walter Jauch, Lu Zhao, Roland Hartig, Peter Camaj, Yue Zhao, Josef Mysliwietz, Qi Bao, Peter J. Nelson, B. Schwarz, Makus Guba, Joachim W. Ellwart, Christiane Bruns |
| المصدر: | Int. J. Oncol. 49, 99-110 (2016) International Journal of Oncology |
| بيانات النشر: | Spandidos Publ Ltd, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, verapamil, Gemcitabine, P-glycoprotein, Side Population, Verapamil, Apoptosis, Pharmacology, Equilibrative nucleoside transporter 1, Equilibrative Nucleoside Transporter 1, 03 medical and health sciences, Mice, 0302 clinical medicine, Side population, Pancreatic cancer, medicine, Cytotoxic T cell, Animals, Humans, ATP Binding Cassette Transporter, Subfamily B, Member 1, Side-Population Cells, Cell Proliferation, biology, Oncogene, gemcitabine, Articles, medicine.disease, Xenograft Model Antitumor Assays, Gene Expression Regulation, Neoplastic, Pancreatic Neoplasms, 030104 developmental biology, Oncology, Tumor progression, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, biology.protein, side population, medicine.drug |
| الوصف: | Tumor side population (SP) cells display stem-like properties that can be modulated by treatment with the calcium channel blocker verapamil. Verapamil can enhance the cytotoxic effects of chemotherapeutic drugs and multidrug resistance by targeting the transport function of the P-glycoprotein (P-gp). This study focused on the therapeutic potential of verapamil on stem-like SP tumor cells, and further investigated its chemosensitizing effects using L3.6pl and AsPC-1 pancreatic carcinoma models. As compared to parental L3.6pl cells (0.9±0.22%), L3.6pl gemcitabine-resistant cells (L3.6plGres) showed a significantly higher percentage of SP cells (5.38±0.99%) as detected by Hoechst33342/FACS assays. The L3.6plGres SP cells showed stable gemcitabine resistance, enhanced colony formation ability and increased tumorigenicity. Verapamil effectively inhibited L3.6plGres and AsPC-1 SP cell proliferation in vitro. A pro-apoptotic effect of verapamil was observed in L3.6pl cells, but not in L3.6plGres cells, which was linked to their differential expression of P-gp and equilibrative nucleoside transporter-1 (ENT-1). In an orthotopic pancreatic cancer mouse model, both low and high dose verapamil was shown to substantially reduce L3.6plGres-SP cell tumor growth and metastasis, enhance tumor apoptosis, and reduce microvascular density. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c42f6ba54c7fbf82fd16125b339e8edbTest https://push-zb.helmholtz-muenchen.de/frontdoor.php?source_opus=48593Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c42f6ba54c7fbf82fd16125b339e8edb |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |