| Icariin potentiates the antitumor activity of gemcitabine in gallbladder cancer by suppressing NF-κB. | |
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MedLine Citation:
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PMID: 23274410 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Aim:Gemcitabine has been increasingly prescribed for the treatment of gallbladder cancer. However, the response rate is low. The aim of this study is to determine whether icariin, a flavonoid isolated from Epimedi herba, could potentiate the antitumor activity of gemcitabine in gallbladder cancer.Methods:Human gallbladder carcinoma cell lines GBC-SD and SGC-996 were tested. Cell proliferation and apoptosis were analyzed using MTT assay and flow cytometry, respectively. The expression of apoptosis- and proliferation-related molecules was detected with Western blotting. Caspase-3 activity was analyzed using colorimetric assay, and NF-κB activity was measured with ELISA. A gallbladder cancer xenograft model was established in female BALB/c (nu/nu) mice. The mice were intraperitoneally administered gemcitabine (125 mg/kg) in combination with icariin (40 mg/kg) for 2 weeks.Results:Icariin (40-160 μg/mL) dose-dependently suppressed cell proliferation and induced apoptosis in both GBC-SD and SGC-996 cells, with SGC-996 cells being less sensitive to the drug. Icariin (40 μg/mL) significantly enhanced the antitumor activity of gemcitabine (0.5 μmol/L) in both GBC-SD and SGC-996 cells. The mice bearing gallbladder cancer xenograft treated with gemcitabine in combination with icariin exhibited significantly smaller tumor size than the mice treated with either drug alone. In GBC-SD cells, icariin significantly inhibited both the constitutive and gemcitabine-induced NF-κB activity, enhanced caspase-3 activity, induced G(0)-G(1) phase arrest, and suppressed the expression of Bcl-2, Bcl-xL and surviving proteins.Conclusion:Icariin, by suppressing NF-κB activity, exerts antitumor activity, and potentiates the antitumor activity of gemcitabine in gallbladder cancer. Combined administration of gemcitabine and icariin may offer a better therapeutic option for the patients with gallbladder cancer. |
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Authors:
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Dian-Cai Zhang; Jin-Long Liu; Yong-Bin Ding; Jian-Guo Xia; Guo-Yu Chen |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-12-31 |
Journal Detail:
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Title: Acta pharmacologica Sinica Volume: - ISSN: 1745-7254 ISO Abbreviation: Acta Pharmacol. Sin. Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-12-31 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100956087 Medline TA: Acta Pharmacol Sin Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of General Surgery, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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