| Objective:Artemether (Artemether) for artemisinin liposoluble derivatives in the clinical treatment of falciparum malaria and cerebral malaria has remarkable curative effect. In recent years, the study found that artemisinin and its derivatives have definite antitumor and inhibit tumor angiogenesis. On the basis of artemisinin and its derivatives with antitumor and inhibition of tumor angiogenesis, and through the blood brain barrier into the brain tissue pharmacokinetic characteristics of, the study of artemether role in human glioma in vitro and in vivo effect. For the treatment of glioma provides a new way of thinking and means.Method:Cultured glioma cell line U251 in vitro and drug artemether text after divided into two groups:ART group and control group. MTT method were used to detect each cell proliferation and inhibition; trans well assay for the detection of two groups of cell invasion and migration ability; using transmission electron microscopy and flow cytometry to two groups of cells apoptosis of qualitative and quantitative detection; by Western blotting of two groups of cells in the target gene (Bcl-2, VEGF and MMP-2, MMP-4, MMP-9, and c-MET,API5)protein expression were detected. The mice were divided into two groups:group of the mice, the group of the mice in the group of Artemisia ether group, the control group and the negative control group. Continuous administration by gastric lavage. The survival state of each group was observed, the body weight and tumor volume were recorded, and the tumor inhibition rate was calculated and the tumor inhibition rate was compared. Tumor tissues were stained with hematoxylin eosin staining (HE staining) and immunohistochemistry, mice tumor growth and vascular endothelial generated in the expression of tumor cells.Results:1, Artemether inhibited the proliferation of glioma cell line U251 follows a linear trend (P<0.05). Control group and ART group compared to dosing group cell growth, proliferation, migration and invasion of ability has been significantly inhibited, and cell apoptosis rate increased, and the occurrence of the Go/Gi phase cell cycle arrest and statistical difference significantly (P< 0.05).2, mice subcutaneous model results that artemether optimum dose group of mice is good, high dose group mice compared with Dimi situation, negative control group mice showed inactive state.From the volume and size of tumor result showed that high dose group and the optimum dose group showed little difference, two groups of tumor volume and size are compared with negative control group, the difference was significant (P< 0.05), but high dose group have a bad state in mice.3, HE staining showed that the brain glioma cells in the negative control group were concentrated in clusters, which showed a short spindle or irregular shape, and showed invasive growth to the brain tissue. The tumor cell density was significantly higher than other experimental groups. The blood vessel density in the negative control group was higher than that in other experimental groups, the result showed that the blood vessel density of the negative control group was higher than that of other groups.Conclusions:Artemethercan inhibited the expression of target gene VEGF, MMP-2, MMP-4, MMP-9, c-MET, Bcl-2,API5 and the proliferation, metastasis and migration of the tumor cells, and participate in the regulation mechanism of the apoptosis of glioma cells. Artemether can inhibit tumor cell proliferation and metastasis mechanism is through the blood brain barrier and inhibits blood vessel formation. Provides a basis in the clinical treatment of development with artemether and another shows the artemisinin and its derivatives not only have antimalarial activity, also has a broad spectrum of antitumor effect. |
PDF Full Text Request