Inhibitory Effects Of Gambogic Acid On Cell Proliferation And Inducing Apoptosis In Mantle Cell Lymphoma

[Objective] To study the mechanisms in gambogic acid (GA)-induced JeKo-1human Mantle Cell Lymphoma cell apoptosis in vitro.[Methods] the proliferation of GA-treated Jeko-1cells was measured by CCK-8assay and ki-67immunocytochemical detection. Appotosis, cell cycle and mitochondrial membrane potential were measured by flow cytometric analysis. Caspase-3,-8and-9were detected by colorimetric assay. Bcl-2and Bax were analyzed by Western blot.[Results]1. GA inhibited Jeko-1cells’ growth in a time-and dose-dependent manner. Lower GA concentration (0.065、0.125、0.25μg/ml) could not inhibit the proliferation of Jeko-1cells(P>0.05). Higher GA(0.5、1.0、2.0、4.0μg/ml) concentrationcould inhibit the proliferation of Jeko-1cells (P<0.05).2. GA did not significantly influence the cell cycle of Jeko-1cell lines at the concentration of0、0.5、1.0、2.0、4.0μg/ml for24h.3. The typical apoptosis morphology change could be visualized after Jeko-1cell lines were incubated with GA. GA induces apoptosis in Jeko-1cells, which was involved in reducing the membrane potential of mitochondria,4. GA increased the apoptosis rate of Jeko-1cell line and increased activated caspase-3, caspase-8, caspase-9positive cell number for different degree in24h.5. There was a significant decrease in Bcl-2expression and increase in Bax expression in a dose-dependent manner after the GA treatment on Jeko-1cell for24h. Compared with the control group, with the concentration of1ug/ml, ratio between Bax and Bcl-2protein increased significantly (P<0.05).[Conclusion]1. GA has inhibitive effect on Jeko-1cell lines’ growth in a concentration dependent manner in vitro.2. GA induces apoptosis on Jeko-1cell lines in a concentration dependent manner. The Mechanism is through the mitochondrial pathway and membrane receptor pathway induce Jeko-1cell apoptosis.The cell cycles are not disturbed obviously in Jeko-1cell lines.3. GA induced apoptosis in human MCL Jeko-1cells by regulating Bcl-2/Bax and activating caspase-3,-8and-9via mitochondrial pathway without affecting cell cycle.