| Interferon-alpha (IFN-α) modulates the chemosensitivity of CD133-expressing pancreatic cancer cells to gemcitabine. | |
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MedLine Citation:
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PMID: 22320450 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Pancreatic cancer is a lethal disease as current chemotherapies with gemcitabine (GEM) are still insufficient. Accumulating evidence suggests that cancer stem cells (CSCs) are responsible for chemoresistance and CD133 is one of the CSC markers in pancreatic cancer. Interferon-alpha (IFN-α), a cytokine with pleiotropic effects, possesses direct cytotoxic and cytostatic effects on tumor cells. The aim of this study was to investigate whether IFN-α can modulate the chemosensitivity of a human pancreatic cancer cell line, Capan-1, to GEM. Cell cycles were evaluated for response to GEM with and without IFN-α by BrdU assay. GEM inhibited Capan-1 cell growth in a dose-dependent manner. GEM (IC(50) ; 100ng/mL) treatment reduced the number of both CD133(+) and CD133(-) cells in S phase, induced apoptosis of CD133(-) cells more than that of CD133(+) cells, and increased accumulation of CD133(+) cells into G0/G1 phase. These results infer that CD133(+) cells shelter into G0/G1 phase by GEM treatment. IFN-α modulated CD133(+) cells from G0/G1 phase to S-phase. Consequently, apoptosis was accelerated in both CD133(+) and CD133(-) cells after IFN-α combined with GEM treatment. Furthermore, GEM combined with IFN-α treatment showed a significant tumor suppressive effect in the in vivo study. Importantly, CD133(+) cells showed CSC-like properties such as generation of spheres, highly invasive ability and high tumorigenesis. These results suggest that IFN-α, as a modulator, could contribute to the treatment of CD133(+) cancer cells and be effective in combined chemotherapies with GEM for pancreatic cancer stem-like cells. © 2012 Japanese Cancer Association. |
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Authors:
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Tomomi Hayashi; Qiang Ding; Taisaku Kuwahata; Koki Maeda; Yumi Miyazaki; Shuichiro Matsubara; Toru Obara; Shoji Natsugoe; Sonshin Takao |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-2-9 |
Journal Detail:
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Title: Cancer science Volume: - ISSN: 1349-7006 ISO Abbreviation: - Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-2-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101168776 Medline TA: Cancer Sci Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2012 Japanese Cancer Association. |
Affiliation:
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Cancer and Regenerative Medicine, Frontier Science Research Center; Department of Digestive Surgery, Kagoshima University Graduate School of Medical and Dental Sciences 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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