腺病毒介导的大鼠增殖抑制基因抑制大鼠胶质瘤的生长

Adenovirus-mediated rat hyperplasia suppressor gene inhibits the growth of glioma in rates

目的:探讨腺病毒介导的大鼠增殖抑制基因(rat hyperpla siasuppressor gene,rHSG)对大鼠胶质瘤生长的抑制作用。方法:建立大鼠C6胶质瘤动物模型,分别在接种C6胶质瘤细胞后第4和11天,于肿瘤原位注射0.9%氯化钠溶液(对照组)、重组腺病毒Adv-rHSG-GFP和腺病毒Adv-GFP,并于接种C6胶质瘤细胞后第9、15和21天取脑胶质瘤观察肿瘤的生长情况,免疫组织化学法检测增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)和rHSG蛋白的表达以及微血管密度(microvessel density,MVD),RT-PCR和蛋白质印迹法检测rHSG mRNA及蛋白的表达。结果:Adv-rHSG-GFP组肿瘤体积明显小于对照组和Adv-GFP组(P<0.01)。Adv-rHSG-GFP组PCNA标记指数和MVD均低于对照组和Adv-GFP组。Adv-rHSG-GFP组rHSG mRNA和蛋白的相对表达量均明显高于对照组和Adv-GFP组(P<0.01)。结论:Adv-rHSG-GFP能够抑制胶质瘤血管生成和肿瘤细胞增殖,对恶性胶质瘤的生长具有明显的抑制作用。

Objective： To investigate the inhibitory effect of adenovirus mediated-rat hyperplasia suppressor gene （rHSG） on the growth of glioma in rats. Methods： A model of rat glioma was established by injection with glioma C6 cells. On the fourth and eleventh days after injection with glioma C6 cells, 0.9% sodium chloride solution （as a control）, Adv-rHSG-green fluorescence protein （GFP） or Adv-GFP was injected into the brain tumors in rats. Then the glioma in rats was removed on the ninth, fifteenth and twenty-first days, respectively, and the tumor growth was observed. The expressions of proliferating cell nuclear antigen （PCNA） and rHSG proteins as well as microvessel density （MVD） were detected by immunohistochemistry. The expression levels of rHSG mRNA and protein were detected by RT-PCR and Western-blotting, respectively. Results： The volume of cerebral glioma in the Adv-rHSG-GFP group was significantly smaller than those in the control and the Adv-GFP groups （P 〈 0.01）. PCNA labeling index and MVD value of the cerebral glioma in the Adv-rHSG-GFP group were both lower than those in the control and the Adv-GFP groups （P 〈 0.01）, while the expression levels of rHSG mRNA and protein were both higher than those in the control and the Adv-GFP groups （P 〈 0.01）. Conclusion： Adv-rHSG-GFP may suppress the angiogenesis and the proliferation of glioma cells, and exerts an inhibitory effect on the growth of glioma.