The Experimental Study On Inhibiting Effect Of Ultrasound Irradiated Microbubbles Combined With Adriamycin On H22 Transplantation Tumor In Mice

Part1 An experimental research into ultrasound combined with nano/microbubbles enhancing the inhibiting effect of Adriamycin on H22 transplantation tumor in miceObjective To investigate ultrasound(US) irradiation combined with nano/microbubble(NMB) whether enhancing the inhibiting effects of adriamycin on H22 hepatocarcinoma in mice or not.Methods 50 models of transplanted subcutaneously tumors in female KM mice were randomly divided into five groups,ten mice in every group:the control group,Adriamycin(ADM) group,ADM+NMB group,ADM+US group, ADM+NMB+US group. The mice were treated every other day for five times. The growth of the tumor was monitored by ultrasound and drawn tumor growth curve diagram.Half of the tumors were extracted for HE staining and CD34 immumohistochemical staining to observe and count the necrosis area and the microvascular density. The remained mice were fed as usual to observe the survival time.Results Compared with the control group, treatment group tumors grew slowly, the lifespan lengthened, the tumor's necrosis area increased, the microvascular density decreased(p<0.05), and the difference of the ADM+NMB+US group is more significant compared with the other experience groups(P<0.05).Conclusions Ultrasound combined with nano/microbubbles can inhibit the growth of H22 subcutaneous transplanted tumor in mice, and it has synergistic inhibition effect with adriamycin.Part2 The exploration on the therapeutic dose and toxicity of adriamycin on H22 transplantation mice combined with ultrasound nano/microbubblesObjective To investigate the dosage and toxic relationship of ultrasound mediated nano/microbubbles(NMB) combined with Adriamycin(ADM) on the treatment of H22 transplanted mice model.Methods 30 models of transplanted subcutaneously tumors in female KM mice were randomly divided into 5 groups(n=6): the control group,ADM 1.0mg/kg,1.5mg/kg,2.5mg/kg groups and 1.0mg/kg ADM + NMB +US group.The mice were treated every other day for five times.The growth of the tumor was monitored by ultrasound and drawn tumor growth curve diagram.The tumor was extracted for HE staining,CD34 and ki67 immumohistochemical staining to observe and count the necrosis area,the microvascular density and the proliferation of tumor cells after finished the treatment and sacrificed the mice.The myocardial enzymes(AST,CK,LDH) were assayed to evaluate the cardiac toxicity of each treatment in mice.Results Compared with the control group,the all experiment groups were with a tumor growth slowly, necrosis area enlargement, microvascular density and the tumor cell proliferating phase decreased(p<0.05). The tumor's volume, microvascular density and the tumor cell proliferating phase of the 1.0mg/kg ADM+NMB+US group were less than all groups(p<0.05) other than 2.5mg/kg ADM group(p>0.05).The values of AST,CK and LDH of 1.0mg/kg ADM+NMB+US group were less than 2.5mg/kg ADM group(p<0.05),but compared with 1.0mg/kg ADM group,there were no statistical differences(p>0.05).The CK of 1.0mg/kg ADM+NMB+US group was less than 1.5mg/kg ADM group(p<0.05).Conclusions Ultrasound irradiation combined with nano/microbubbles can keep the therapeutic effect of adriamycin but decrease the dose and toxicity on H22 transplanted mice.