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Nawara, Hend M. Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
Afify, Said M. Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University ORCID
Hassan, Ghmkin Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University ORCID
Zahra, Maram H. Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
Atallah, Marwa N. Vertebrates Embryology and Comparative Anatomy, Zoology Department, Faculty of Science, Menoufia University
Mansour, Hager Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
Abu Quora, Hagar A. Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
Alam, Md Jahangir Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
Osman, Amira Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
Kakuta, Hiroki Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences ORCID Kaken ID publons researchmap
Hamada, Hiroki Department of Life Science, Faculty of Science, Okayama University of Science
Seno, Akimasa Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University ORCID Kaken ID publons researchmap
Seno, Masaharu Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University ORCID Kaken ID publons researchmap
Abstract
Combination therapy, which is a treatment modality combining two or more therapeutic agents, is considered a cornerstone of cancer therapy. The combination of anticancer drugs, of which functions are different from the other, enhances the efficiency compared to the monotherapy because it targets cancer cells in a synergistic or an additive manner. In this study, the combination of paclitaxel and sorafenib in low concentration was evaluated to target cancer stem cells, miPS-BT549cmP and miPS-Huh7cmP cells, developed from mouse induced pluripotent stem cells. The synergistic effect of paclitaxel and sorafenib on cancer stem cells was assessed by the inhibition of proliferation, self-renewal, colony formation, and differentiation. While the IC(50)values of paclitaxel and sorafenib were approximately ranging between 250 and 300 nM and between 6.5 and 8 mu M, respectively, IC(50)of paclitaxel reduced to 20 and 25 nM, which was not toxic in a single dose, in the presence of 1 mu M sorafenib, which was not toxic to the cells. Then, the synergistic effect was further assessed for the potential of self-renewal of cancer stem cells by sphere formation ability. As a result, 1 mu M of sorafenib significantly enhanced the effect of paclitaxel to suppress the number of spheres. Simultaneously, paclitaxel ranging in 1 to 4 nM significantly suppressed not only the colony formation but also the tube formation of the cancer stem cells in the presence of 1 mu M sorafenib. These results suggest the combination therapy of paclitaxel and sorafenib in low doses should be an attractive approach to target cancer stem cells with fewer side effects.
Keywords
cancer stem cells
combination therapy
paclitaxel
sorafenib
Published Date
2020-05-26
Publication Title
Cancers
Volume
volume12
Issue
issue6
Publisher
MDPI
Start Page
1360
ISSN
2072-6694
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
Copyright Holders
© 2020 by the authors.
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isVersionOf https://doi.org/10.3390/cancers12061360
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http://creativecommons.org/licenses/by/4.0/