Effects Of HIFU Combined With Localized Chemotherapy On Apoptosis And Proliferation Of U251 Gliomas In Nude Mice

Objective:Human glioma(U251) subcutaneous models in nude mice was set as a research platform.Localized chemotherapy and/or high inensity focused ultrasound(HIFU) ablation were given respectively.After the treatment,the volume of tumors was measured and the pathological characteristics,apoptosis and proliferating cell nuclear antigen(PCNA) in tumor tissues were tested respectively.It mainly focuses the role about the treatment of HIFU combined with chemotherapy on subcutaneous glioma,which provided a new method to enhance HIFU effects.Methods:Logarithmic phase U251 glioma cell suspension was inoculated into the bilateral hip subcutaneous tissue of 15 nude mice, human glioma(U251) subcutaneous models in nude mice was established. 28 days later,the longest diameter of tumors ranged from 1.0 to 1.2 centimeter.These nude mice bearing subcutaneous human neuron-gliocytoma xenografts were divided into three groups randomly,i.e. HIFU in combination with ACNU(Nimustine) adjuvant themotherapy group,single chemotherapy group and single HIFU group.The CZF-Ⅱextracorporeal HIFU with 9.7MHz transducer(focal length:4.5 mm, focal intensity:2 500 W/cm~2) was adopted in the experiment.The growth curves in three groups were mapped.The pathological characteristics,apoptosis and PCNA in tumor tissues were tested by HE staining examination,TdT-mediated UTP nick end labeling(TUNEL) and immunohistochemical staining respectively.Results:Tumor formation rate was 100%,and human glioma(U251) subcutaneous models in nude mice was established.24 hours after HIFU ablation,coagulatied necrosis in the target area was formed.In the periphery of the target area,the percentage of PCNA in the HIFU in combination with chemotherapy group was significantly less than that in single chemotherapy group and single HIFU group(P＜0.01),and the number of apoptosis cells was more than the other two groups(P＜0.01).7 days later,the volume of tumor tissues in HIFU in combination with ACNU group was smaller than that in single chemotherapy group and single HIFU group(P＜0.01).Conclusion:In the periphery of the target area,HIFU in combination with adjuvant chemotherapy could enhance the HIFU therapeutic effects obviously,and also induce U251cell apoptosis and restrain its proliferation in glioma,thus it would promote the therapeutic efficacy of glioma.There were marked synergstic effects of both HIFU ablation and chemotherapy on U251 glioma in nude mice.