Neomycin Combined With Sodium Phenylbutyrate Inhibits The Growth Of Glioma

Neomycin combined with sodium phenylbutyrate inhibits the growth of gliomaIntroductionGlioma is the most common one of the primary central nervous system malignancies. Malignant gliomas are responsible for 2.5% of cancer deaths in the United States. This heterogeneous group of diseases represents 1% of adult cancers, the most common solid tumors in children, and the third leading cause of cancer death in the 15 to 34 age group. Hence, although relatively rare, malignant primary brain tumors result in a substantial number of person-years of lives lost. Because the boundary of it is not clear and the growing pattern of it likes that of tree root, resecting of it can only reach the degree of subtotal. So the recurring of glioma after the therapy is inevitable. Because of the speciality of the intracranial environment, the most cytotoxicity drugs is less effective, on the other hand, the inhibitory effect to the bone marrow limited the usage of it. The development of radiosurgery has controlled the growth of benign tumor effectively, but when confronted to the glioma, its ability would be small and weak.The growth of tumor is dependent on the angiogenesis. The tumor itself needs vessels to deliver the results of metabolism and oxygen. This theory has been documented: the tumor can be controlled after the growth of its new vessel was inhibited. It is documented that neomycin can prevent the translocation of several VEGF and thereby can inhibit the angiogenesis of tumor. In the recent years, differentiation therapy boomed. Retinoic acid has been managed successfully to cure acute promyelocytic leukemia, which has inspired many oncologist greatly. In the literature we find that sodium phenylbutyrate can induce the differentiation of glioma clearly: the glioma cells gradually lost its malignant appearance, the rate of proliferation declined and apoptosis can be found clearly. This paper use the Fischer344 rats and F98 glioma cell lines as animol model, employ neomycin and phenylbutyrate to treatment this tumor. The effect of this drug will be observed and the mechanism will be analyzed.Part I Neomycin combined sodium phenylbutyrate inhibit growth of glioma in vitroObjectives: To explore the inhibitory effect of different concentration of neomycin, phenylbutyrate and both to the F98 glioma cells and accumulate data for the experiment in vivo by the way.Methods: F98 glioma cells were cultured according to the routine. First employ the cells which grow in a pattern of logarithm into the culture plate. Managed to make the concentration of these drugs as 0, 2.5, 5 and 10 mmol L-1. Going on with the culture until 72 hours passed, all the specimen is observed under the wave length of 570 nm. The inhibitory rate is calculated as follows:IR = (1-experimental OD value /controlling OD value)*100% The OD value and the IR were described as means + SD. The two-Way ANOVA analysis is used to assess the effect of inhibition.Results: After the culture of 72 hours, it has been showed that neomycin inhibited the growth (when the concentration changes from 2.5 to 5 to 10 mmol-L-1, the IR changes from 0.13+0.05 increased to 0.25+0.06 to 0.37+0.03, P<0.05) ; Phenylbutyrate inhibited the growth of glioma significantly (when the concentration changes from 2.5 to 5 to 10 mmol-L-1, the IR changes increased from 0.23+0.06 to 0.46+0.09 to 0.66+0.08, PO.01); The combination of both inhibited much significantly (when the concentration changes from 2.5 to 5 to 10 mmol-L-1, the IR changes increased from0.31+0.05 to 0.55+0.08 to 0.80+0.06, P<0.01).Conclusion: Both neomycin and phenylbutyrate inhibited the growth of glioma significantly. The combination of these two drugs seemed to have a synergy effect of inhibition. The mechanism of neomycin may be involved the blockage of the translocation of aFGF and bFGF. The inhibitory effect of phenylbutyrate maybe relates the induction of apoptosis and cell differentiation.