| This paper reports the primary in vitro anticancer activity of macrolides derivates detected using a panel of cultured human tumor cell lines,and focus on the study of the anticancer activity of EMD642,one of effective derivates,in vitro and in vivo.The mechanism of EMD642 is also investigated.To assess the anti-proliferation effect of macrolides derivates,experiments with MTT method were performed in vitro.The results express that majority if the derivates inhibited the proliferation of human gastric adenocarcinoma SGC-7901 cells, human fibrosarcoma cell HT1080 cells and human oral carcinoma cell KB cells.Their 50%inhibitive concentrations(IC50)are lower/correspond to cisplatin.The results demonstrate that EMD642,VVB0412,EMD603,EMD607,VVB-031 are worth to be further developed.Following,under invert microscope we observed the typical morphological changes of apoptosis cells when incubated with EMD642.This strongly hinted us that EMD642 might exert its anticancer activity through triggering tumor cell apoptosis. So we studied the morphological and biochemical characteristics of tumor cell after treated with EMD642.Optic microscope and fluorescence microscope photomicroscopical observation show that EMD642 induced cell apoptosis in SGC-7901.Cell cycle was analyzed by flow cytometer.Conclusion that cell cycle was arrested at G0/G1 period,and then cells were induced apoptosis can be educed. Moreover,we studied on the in vivo anti-tumor effect of EMD642,the tumor growth of mice with S180was inhibited compared with the control group after animals were treated with EMD642 i.p.at 5,10,20 mg·kg-1·d-1for 7 days,and the average tumor suppression rates were higher/correspond to CTX.In conclusion,the present thesis first studied on the anticancer effect of EMD642,in vitro and in vivo.We demonstrated that the anticancer mechanism of it is because of inducing tumor cells apoptosis.Our research can be helpful to the development of EMD642 to anticancer drug in the future.
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