Shikonin Induces Apoptosis And G0/G1 Phase Arrest Of Gallbladder Cancer Cells

Objective: Gallbladder cancer(GBC)is a prevalent biliary tract malignancy,and the prognosis for GBC is extremely poor.However,it’s usually too late to diagnose GBC because of the lack of specific symptoms.The only curative therapy for GBC is surgical resection.Thus,the identification of novel and promising agents for the treatment of GBC is urgently needed.Methods: The MTT assay,cell colony formation assay and flow cytometry assay were performed to investigate the effects of shikonin on GBC cell lines.The change of expression levels of apoptosis-related proteins of GBC cells were detected via western blot assay.The xenograft tumors in nude mice were established to confirm the apoptotic effects of shikonin,and the proteins expression level of tumors were determined by western blot to further verify the effects.Results: The results of MTT and colony formation assay suggest that shikonin can induce apoptosis of GBC cell lines,which were also verified by the results of flow cytometry and Hoechst 33342 staining.The results of western blot showed that shikonin may induce apoptosis of GBC cells via JNK signal pathway.The results of flow cytometry assay showed that shikonin can regulate the cell phase of GBC cells,the western blot assay furtherly confirmed that shikonin induce the G0/G1 phase arrest.Shikonin can also inhibit the tumor growth in time and dose dependent manner in vivo.Conclusions: Shikonin may induces apoptosis of GBC cells via JNK signaling pathway,it could be a novel and safe chemotherapeutic agent for the treatment of GBC.