局部热化疗对大鼠皮下移植胶质瘤细胞增殖和血管再生的影响  

Effects of localized thermochemotherapy on angiogenesis and proliferation of C6gliomas in rats

作　　者：谭社练[1] 欧英雄[1] 赵伯端[1] 方胜[1] 杨本生[1] 赵鹏洲[1] 

机构地区：[1]广东省江门市人民医院神经外科,江门529051

出　　处：《第二军医大学学报》2004年第7期773-776,共4页Academic Journal of Second Military Medical University

摘　　要：目的 :研究局部热化疗对大鼠皮下移植胶质瘤血管再生的影响 ,探讨其作为胶质瘤辅助治疗的可行性。 方法 :将传代培养的 C6细胞接种于大鼠背部皮下 ,肿瘤生长至 1 .5～ 2 cm直径时 ,分组进行局部热疗、化疗和热化疗。继续观察皮下肿瘤生长情况 ,测量瘤体体积和质量 ;用免疫组化 S- P法检测增殖细胞核抗原 (PCNA)、胰岛素样生长因子 (IGF- )、血管内皮生长因子 (VEGF)蛋白表达 ;用因子 相关抗原 (F - RA)染色标记血管内皮细胞 ,以微血管密度 (MVD)作为定量检测指标。用 H- E染色法、电镜观察肿瘤增殖状况和肿瘤微血管结构的变化。结果 :热疗、化疗、热化疗与对照组比较 :瘤体缩小 ,质量减轻 ;PCNA、IGF- 、VEGF蛋白表达降低 (P<0 .0 1 ) ,MVD降低 (P<0 .0 1 ) ,且热化疗较单纯热疗和化疗降低更明显 (P<0 .0 1 )。热化疗后肿瘤细胞增殖明显受抑制 ,微血管外径变小 ,血管壁变厚 ,血管减少 ,血管内皮细胞紧密连接增多 ,细胞连接间隙减小 ,有的血管甚至只能发现完整的基膜而缺乏内皮细胞。结论 :热疗、化疗、热化疗能抑制肿瘤血管再生与肿瘤增殖 ,且热化疗有协同作用 ;热化疗抑制胶质瘤的 PCNA合成与表达、以及抑制 IGF- 的合成与分泌是其抑制肿瘤增殖的机制之一 ;热化疗能降低肿瘤 VEGF合成与分泌 。Objective:To study the effects of local thermochemotherapy on angiogenesis and proliferation of C6gliomas in rats,and to explore the feasibility of using it as a new therapeutic method for gliomas.Methods:C6glioma cells were in-jected subcutaneously into rats,which were randomly assigned into4groups and treatment were initiated on22d after tumor inoculation.When the tumor diameter reached1.5to2.0cm,local thermochemotherapy,hyperthermia and chemotherapy were given respectively.The volume and weight of subcutaneous tumor were measured;PCNA,IGF-Ⅰ,VEGF and FⅧ-RA protein expression were measured by S-P immunohistochemical staining.Glioma cells proliferation were measured by H-E staining and electron-microspic technique.The vascular structure in rat glioma were measured by immunohistochemical stain-ing and electronmicroscopy technique.Results:Compared with the control group,the tumor volume of hyperthermia,chemotherapy and thermochemotherapy groups were decreased(P<0.01).The expression of PCNA,IGF-Ⅰand VEGF pro-tein were decreased,and MVD were decreased too(P<0.01).Electron-microspic method showed that proliferation and an-giogenesis were inhibited by interstitial localized-thermochemotherapy in rat gliomas.Conclusion:Hyperthermia,chemothera-py and thermochemotherapy inhibits tumor angiogensis and proliferation.Adriamycin(ADM)has marked synergistic effects with hyperthermia in C6glioma of rats.One of mechanisms of proliferation inhibition is the decreased expression of PCNA and IGF-Ⅰprotein.The mechanisms for angiogenesis inhibition are decreased VEGF expression,microvessel damage,and de-creased tumor MVD.Thermochemotherapy may be a therapeutical method for gliomas.

关 键 词：胶质瘤 热化学疗法 血管再生 细胞增殖 

分 类 号：R730.264[医药卫生—肿瘤]