Guggulsterone enhances antitumor activity of gemcitabine in gallbladder cancer cells through suppression of NF-κB

Purpose: Patients with gallbladder cancer usually have a poor prognosis, and effective standard chemotherapeutic regimens have not been established. The anticancer activities of guggulsterone have been demonstrated in various cancer cells. The aims of the study were to determine the effect of guggulsterone on gallbladder cancer cells and to investigate whether treatment with guggulsterone influences the antitumor activities of gemcitabine. Methods: The Dojindo Cell Counting Kit-8 assay was used to determine the inhibition of proliferation by drugs in TGBC1 and TGBC2 cells. Cell migration and invasion were examined using 24-well inserts and Matrigel^TM-coated invasion chambers. The activities of NF-κB p65, VEGF-C, and MMP-2 were measured by ELISA. Results: Guggulsterone inhibited the proliferation and suppressed migration and invasion of gallbladder cancer cells in a dose-dependent manner. Guggulsterone significantly decreased NF-κB p65, VEGF-C, and MMP-2 activities in the gallbladder cancer cells examined. Gallbladder cancer cells treated with a combination of gug-gulsterone and gemcitabine demonstrated significant inhibition of cell proliferation and invasion when compared to treatment with gemcitabine alone. In addition, NF-κB p65 activation decreased significantly in cells treated with a combination of guggulsterone and gemcit-abine when compared to treatment with gemcitabine alone. Conclusions: Guggulsterone exhibits anticancer activities and enhances the antitumor activities of gemcitabine through the suppression of NF-κB activation in gallbladder cancer cells. These results suggest that guggulsterone could be a potential therapeutic option for patients with gallbladder cancer.