title: PI3K/Akt is involved in bufalin-induced apoptosis in gastric cancer cells.
abstract: Bufalin is the active ingredient of the Chinese medicine Chan Su, and it has been reported that bufalin induces apoptosis in some human leukemia and solid cancer cell lines. The exact mechanism of bufalin-induced apoptosis is, however, still not clear. In this study, we demonstrated that bufalin inhibited the proliferation of gastric cancer MGC803 cells in a dose-dependent and time-dependent manner. At a low concentration (20 nmol/l), bufalin induced M-phase cell cycle arrest, whereas at a high concentration (80 nmol/l) it induced apoptosis in MGC803 cells. Bufalin increased the Bax/Bcl-2 ratio and activated caspase-3 during the apoptotic process of MGC803 cells. It should be noted that bufalin transiently activated the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway and then inhibited it completely, and upregulated the Casitas B-lineage lymphoma (Cbl) family of ubiquitin ligases, upstream modulators of PI3K. A combination of bufalin and LY294002, a PI3K-specific inhibitor, enhanced apoptosis, but PD98059, an extracellular-regulated protein kinase-specific inhibitor, had no significant effect on bufalin-induced apoptosis. These results suggested that the PI3K/Akt pathway might play a key role in bufalin-induced apoptosis in gastric cancer MGC803 cells.
authors.affiliation: Department of Medical Oncology, the First Hospital, China Medical University, Shenyang, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Qu
authors.forename: Kezuo
authors.initials: K
authors.lastname: Hou
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qian
authors.initials: Q
authors.lastname: Dong
authors.forename: Yuee
authors.initials: Y
authors.lastname: Teng
authors.forename: Jingdong
authors.initials: J
authors.lastname: Zhang
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Liu