Anti-tumor Activity Of Atractylenolide Ⅰ On Gallbladder Cancer In Vivo And In Vitro Through The JNK-pSmad3L-c-Myc Signaling Pathway

Objective: Gallbladder cancer,a highly aggressive tumor with an extremely poor prognosis,is the most common malignancy of the biliary tract.Atractylenolide Ⅰ(ATR-1),an active component of Rhizoma Atractylodis Macrocephalae and a widely used Chinese herbal medicine,exhibits a wide range of potential anti-tumor activities in many tumor cell lines,such as bladder carcinoma and so on.However,little is known about the precise mechanisms of anti-tumor effects on gallbladder cancer.The aim of our study was to investigate the effects of ATR-1 on gallbladder cancer cells(NOZ and EHGB-1 cells)and the underlying mechanism,which will provide a reliable experimental support for ATR-1 working as a new anti-gallbladder cancer chemotherapy drugs.Methods: In current study,MTT and colony formation assay are used to explore the biological effects of ATR-1 on gallbladder cancer cells;and Annexin V/propidium iodide(PI)double-staining assay,Hoechst 33342 staining assay to investigate the apoptosis effect and Flow cytometric analysis to cell cycle investigation.Meanwhile,we have done the Western blotting analysis to discuss the underlying molecular mechanism.Besides,we investigate the inhibitory effect of ATR-1 in nude mice carrying subcutaneous NOZ tumor xenografts.Results: The ATR-1 inhibits proliferation and viability of gallbladder cancer cells,induces apoptosis and G0/G1 phase arrest.The tumors from the ATR-1 treated mice were obviously smaller and lighter than those in the vehicle group in a dose-dependent manner(within the safe concentration range).Conclusion: ATR-1 inhibits the proliferation of gallbladder cancer cells in vivo and in vitro.Thereby,ATR-1 may be a promising drug for adjuvant chemotherapy in gallbladder cancer.