摘要
目的 探讨局部热化疗对大鼠胶质瘤凋亡、耐药和肿瘤微血管的作用。方法 将C6 细胞接种于大鼠背部皮下 ,肿瘤生长至 1 .5～ 2cm直径时 ,分组进行局部热疗、化疗和热化疗。观察皮下肿瘤生长情况 ;用S P免疫组化法检测bax、bcl 2和 p gp蛋白表达 ;用HE染色法、电镜、TUNWL法观察凋亡 ;电镜观察肿瘤微血管的变化。结果 热疗、化疗、热化疗组较对照组瘤体缩小 ,瘤重减轻 (P <0 .0 0 1 ) ;bax蛋白表达增强 (P <0 .0 0 1 ) ,且热化疗组较单纯热疗和化疗组均增强 (P <0 .0 0 1 ) ;bcl 2蛋白表达改变不明显 (P >0 .0 5 ) ;化疗组 p gp表达增强 (P <0 .0 0 1 ) ,热疗和热化疗组 p gp表达减弱 (P <0 .0 0 1 ) ;细胞凋亡指数增大 (P<0 .0 0 1 ) ;热化疗组出现核染色质凝聚 ,凋亡小体 ;肿瘤微血管外径变小 ,管壁变厚 ,血管减少 ,有的血管甚至只能发现完整的基膜而缺乏内皮细胞。结论 (1 )热疗化疗、热化疗能抑制肿瘤增殖 ,促进bax蛋白表达 ,使bcl 2 /bax减小 ,诱导细胞凋亡 ,且热化疗有协同作用。(2 )化疗能增强细胞耐药 ,使 p gp表达增强 ;而热疗和热化疗均使 p gp表达减弱 ,抑制肿瘤耐药。 (3)热疗可直接损伤细胞和周围血管 ,减低血管密度 ,促进细胞凋亡 ;而凋亡细胞 p gp表达减弱 ,细胞内药物浓度增加 ;阻止?
Objective To study the effects of localized thermochemotherapy on apoptosis and drugresistance as well as angiogenesis of C 6 gliomas in rat.Methods C 6 glioma cells were injected subcutaneously to rats. The rats were randomly assigned to 4 groups, and treatment was initiated on Day 22 after tumor inoculation. Prior to treatment,the subcutaneous gliomas were examined to verify tumor size,which measured range 1.5 to 2.0 cm. Then localized thermochemotherapy, hyperthermia and chemotherapy were given respectively. The volume and weight of subcutaneous tumor were measured. Bax and bcl 2 as well as p gp protein expression were detected by S P immunohistochemical staining. Glioma cells apoptosis or proliferations were detected by TUNEL method and electroscopic technique. The structure of vascular in gliomas were detected by electronscopy technique.Results Compared with the control group,hyperthermia and chemotherapy as well as thermochemotherapy groups,the volume of tumor was decreased,the tumor weights were decreased( P < 0.001 );bax protein expression was increased ( P < 0.001 );bcl 2/bax was decreased. p gp protein expression was increased in chemotherapy group( P < 0.001 ) and decreased in hyperthermia or thermochemotherapy group( P < 0.001 ); Apoptosis index were increased( P < 0.001 ). Electroscopic method also showed that vessel diameter became smaller and basic membrane became thicker.Conclusion (1) Hyperthermia, chemotherapy and thermochemotherapy could inhibit subcutaneously tumor growth and could increase expression of bax protein, decrease bcl 2/bax, induce tumor's apoptosis. Adriamycin(ADM) showed marked synergstic effects with hyperthermia in C 6 glioma of rat. (2) Chemotherapy could increase multidrug resistance of C 6 glioma cells .The postive rate of p gp in C 6 glioma cells increased after chemotherapy. Hyperthermia and thermochemotherapy could decrease expresion of p gp protein, They could inhibit multidrug resistance of C 6 glioma cells in rat. (3) The mechanisms of thermochemotherapy proposed to explain this hyperthermia synergism with ADM,are damaged C 6 glioma cells and microvessels, decreased microvessels density,induced tumor cells apoptosis,decreased expression of p gp protein,increased drug retention in cells, increased DNA damage and decreased DNA repair.
出处
《肿瘤防治研究》
CAS
CSCD
2003年第3期176-179,F002,共5页
Cancer Research on Prevention and Treatment
基金
湖北省 2 0 0 0年重点指令性计划基金资助项目 (2 0 0 2 p1 5 0 8)
