Icariin potentiates the antitumor activity of gemcitabine in gallbladder cancer by suppressing NF-κB

摘要

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-KB activity was measured with ELISA.A gallbladder cancer xenograft model was established in female BALB/c (nuu) 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 G0-G1 phase arrest,and suppressed the expression of Bcl-2,Bcl-xL and surviving proteins.Conclusion: Icariin,by suppressing NF-KB 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.