The Reserch On The Structure And Toxicity Of Cantharidin Derivates And The Inhibition Effects Of Norcantharidin On MGC-803 Cells

At present,a great progress has been made on the structure and the toxicity of cantharidin and its derivates.In present studies,the relationship between the structure and toxicity of cantharidin and its derivates was investigated with the Topkat 6.2 software. Furthermore.in order to investigate the anti-tumor effects of cantharidin derivates on the human MGC-803 cells,the morphological changes,reactive oxygen species(ROS), apoptosis-related protein,and cell cycle arrest in the cells were detected.The calculation of Topkat 6.2 software show that the inhibition effects of cantharidin derivates on phosphatase is related to the toxicity of cantharidin derivates.Moreover,the inhibition effects of cantharidin derivates on phosphatase is increasing with the increasing toxicity of cantharidin derivates,which shows a positive correlation.In our studies,the results of MTT test indicated that the MGC-803 cell apoptosis was induced by 10μg/mL norcantharidin,while cell proliferation was inhibited in a dose dependent manner(p＜0.05).Stained with acridine orange and ethidium bromide(AO/EB), the morphological changes and apoptotic bodies in the MGC-803 cells were detected with fluorescence microscope.In addition,the membrane potential of mitochodria in cells was increased when the MGC-803 cells were treated with 2.5μg/mL NCTD for 24 hours (p＜0.01).However.the membrane potential of mitochodria was decreased when the MGC-803 cells were treated with 12.Sμg/mL NCTD for 24 hours(p＜0.01).When the MGC-803 cells were treated with 10μg/mL NCTD for six hours,the ROS level was increased with its increasing concentration(p＜0.05).At the same time,the activity of T-SOD enzyme was increased.In addition,the expression of Bcl-2 was increased when the MGC-803 cells were treated with low concentration NCTD,but high concentrations of NCTD decreased the expression of Bcl-2(p＜0.01).The expression of Caspases-3 protein was increased as the concentration of NCTD was increased.However, the expression of Caspases-3 protein was decreased in the late apoptosis.Detected by Flow Cytometry,the cell cycle was inhibited and the number of G2/M phase cells was increased.