Experimental Study On Therapeutic Effect Of Small Molecular Compounds (LS) On Glioma In Vivo And In Vitro

Part one:Therapeutic effect of LS on glioma in vitroObjective:To study the therapeutic effect of LS on glioma and screen the best drug for the latter experiments through studying the inhibitory effect of the compound on the growth and migration of HUVEC and U251 cells in vitro.Methods:We observed the inhibitory effect of LS-7,LS-11,LS-13,LS-17 and LS-27in different concentrations on the proliferation rate of HUVEC cells by CCK-8 test;and we analyzed the effect of LS-7,LS-11,LS-13,LS-17 and LS-27 on the migration of U251 cells by scratch test;then we analyzed the effect of LS-13 and LS-17 in different concentrations on the migration capacity of HUVEC cells and U251 cells through Transwell test.Results:The inhibition test on HUVEC cells in vitro:LS-13,LS-17 and LS-27 concentration-dependently inhibited the proliferation of HUVEC cells,LS-13 took the most obvious inhibitory effect,LS-17,weaker,LS-27,the weakest;scratch test:LS-07,LS-13 and LS-17 played an obvious inhibitory effect on the migration of U251 cell in contrast with the control group;Transwell test:LS-13 and LS-17 concentration-dependently inhibited the migration of U251 and HUVEC cells,the inhibitory effect on HUVEC cells of LS-13 and LS-17 was more obvious,LS-13 and LS-17 in iso-concentration played an equivalently inhibitory effect on the migration of U251 and HUVEC cells.Conclusion:LS-13 and LS-17 have an obvious inhibitory effect on the proliferation of HUVEC,and the inhibitory effects are positively correlated with the concentration of drug.LS-13 and LS-17 could inhibit the migration of U251 and HUVEC cells,positively relating to drug concentration,and when the concentration is equal,the inhibitory effect is basically equivalent.Part two:Study on the therapeutic effect of LS-13 on nude mice with subcutaneous xenografts of human gliomaObjective:To study the mono-therapeutic and combined therapeutic effect of LS-13 on the growth of glioma in vivo by establishing a subcutaneous xenograft model in nude mice of human glioma.Methods:We tried to fine out the toxic response of nude mice to LS-13 and LS-17 by single dose toxicity experiments;and we established a nude mice model bearing human glioma subcutaneously and observed the inhibitory effects of LS-13 in different doses on the growth of the subcutaneous tumor in nude mice in order to study the anti-tumor dose-effect relationship of LS-13;taking the nude mice bearing human glioma subcutaneously as model,we researched the inhibitory effect of the combined administration of LS-13 and doxorubicin on the growth of the tumor.Results:Single dose toxicity test:in contrast with the control group,LS-13 and LS-17 group had no significant difference in body weight and clinical manifestation(p>0.05);LS-13 anti-tumor dose-effect test:compared with the model group,there were no significant differences in nude mice weight in the therapeutic groups of different dose(P>0.05);RTV of transplanted tumor in the groups in does of 50mg/Kg and 100mg/Kg were smaller than that in model group(P<0.05);RTV of the tumor in the 12.5mg/Kg dose group was smaller than that in model group after the tenth day(P<0.05);RTV of the tumor in 25mg/Kg dose group was smaller than that in model group after the seventh day(P<0.05);in addition,T/C(%)in the 12.5mg/Kg therapeutic group was more than 40%,implying that the dose was not valid for the tumor in the therapy;while T/C(%)in 25mg/Kg,50mg/Kg and 100mg/Kg groups were less than 40%,implying they were effective in the treatment of tumor.LS-13 combined with doxorubicin drug efficacy trials:differences of the body weight of mice bearing transplanted tumor in LS-13 group,adriamycin group,combined administration group and model group were not statistically significant(P>0.05);after the fifth day,RTV of the tumor in LS-13 group,adriamycin group and combined administration group were all lower than that in model group(P<0.05),and the RTV of the transplanted tumor in combined administration group was less than that in the LS-13 group(P<0.05),and RTV in adriamycin group and combination administration group had no statistical difference(P>0.05);then T/C(%)of each group were calculated,and the results were,respectively,27.31%in LS-13 group,14.49%in adriamycin group,10%in combination administration group,and all the results were valid;in addition,the calculated value of Q was 0.9375,taken as additive synergistic effect.Conclusion:LS-13 has an obvious inhibitory effect on the growth of human glioma tumor transplanted in nude mice subcutaneously,in which therapeutic effect in does of 25mg/Kg,50mg/Kg and 100mg/Kg is the most obvious;compounds LS-13 and Adriamycin combined administration has an additive anti-tumor effect and enhance the therapeutic effect.