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Zhao, L.* ; Zhao, Y.* ; Schwarz, B.* ; Mysliwietz, J. ; Hartig, R.* ; Camaj, P.* ; Bao, Q.* ; Jauch, K.W.* ; Guba, M.* ; Ellwart, J.W. ; Nelson, P.J.* ; Bruns, C.J.*

Verapamil inhibits tumor progression of chemotherapy-resistant pancreatic cancer side population cells.

Int. J. Oncol. 49, 99-110 (2016)
Verlagsversion DOI PMC
Closed
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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 Hoechst 33342/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.
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3.018
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28
30
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Gemcitabine ; P-glycoprotein ; Side Population ; Verapamil; Stem-like Cells; Drug Efflux Capacity; Growth-factor Stimulation; Multidrug-resistance; P-glycoprotein; In-vitro; Mesenchymal Transition; Signal-transduction; Sp Phenotype; Bone-marrow
Sprache englisch
Veröffentlichungsjahr 2016
HGF-Berichtsjahr 2016
ISSN (print) / ISBN 1019-6439
e-ISSN 1791-2423
Quellenangaben Band: 49, Heft: 1, Seiten: 99-110 Artikelnummer: , Supplement: ,
Verlag Spandidos Publ.
Verlagsort Athens
Begutachtungsstatus Peer reviewed
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-501793-001
Scopus ID 84978397791
PubMed ID 27177126
Erfassungsdatum 2016-05-19