TNP-470与卡氮芥抗人U-251胶质母细胞瘤细胞异种移植瘤生长作用的对比研究

Effect of TNP-470 and BCNU on Growth of Human Glioblastoma U-251 Xenografts in Mice

目的比较O-(氯乙酰-氨甲酰基)烟曲霉醇(TNP-470)和卡氮芥(BCNU)对人U-251胶质母细胞瘤细胞裸鼠皮下移植瘤的治疗作用。方法将人U-251胶质母细胞瘤细胞株种植于裸鼠皮下,制备U-251胶质瘤动物模型,第7天荷瘤裸鼠随机分为3组:TNP-470组、BCNU组及对照组。治疗后第21天观察裸鼠体重及肿瘤大小,并测定移植瘤CD105标记的肿瘤微血管密度(CD105-MVD)。结果治疗后第21天①TNP-470组(576.10mm3±114.29mm3)及BCNU组移植瘤体积(473.01mm3±48.04mm3)均明显小于(P<0.01)对照组(1512.61mm3±470.25mm3);TNP-470组与BCNU组间移植瘤体积无显著性差异(P>0.05)。②TNP-470组与BCNU组抑瘤率分别为(61.91%±6.29%)和(68.73%±9.65%),两组相较无明显差异(P>0.05)。③TNP-470组移植瘤CD105-MVD[(5.70±0.85)个/视野]显著低于(P<0.05)BCNU组[(8.60±0.87)个/视野];两治疗组移植瘤CD105-MVD均较对照组[(11.32±1.50)个/视野]显著降低(P<0.05)。结论TNP-470和BCNU对人U-251胶质母细胞瘤细胞裸鼠皮下移植瘤的生长具有相同的抑制作用。

Objective To explore the effect of O-（chloroiacetyl-carbamoyl） fumagillol （TNP-470） and 1, 3-bis （2-chloroerthy）-1- nitrosourea （BCNU） on growth of human glioblastoma U-251 xenografts in nude mice. Methods Human glioblastoma U-251 cell strains were subcutaneously injected in 18 nude mice. The mice were randomly divided into 3 groups on the seventh day after tumors implantation, i.e. TNP-470-treated group, BCNU-treated group and the control group. The tumor size and weights were measuered on the 21th day after the treatment. The microvessel density labled with CD105 （CD105-MVD） in the tumors was determined by immunohistochemical technique. Results （1）The volumes of xenografts in both the TNP-470-treated group （576.10 mm^3±114.29 mm^3） and the BCNU-treated group （473.01 mm^3±48.04 mm^3） were significantly smaller （P〈0.01）than that in the control group （1512.61 mm^3±470.25 mm^3）. There was insignificant difference in the volume of xenografts between TNP-470-treated group and BCNU-treated group （P〉0.05）. （2） There was insignificant difference in the inhibition rate of tumor growth between TNP-470-treated group （61.91%± 6.29%） and BCNU-treated group （68.73%±9.65%） （P〉0.05）. （3） The CD105-MVD of xenografts in TNP-470-treated group [（5.70± 0.85）/HP] was significantly lower （P〈0.05） than that in BCNU-treated group [（8.60±0.87）/HP], and the CD105-MVD of xenografts in both the treated groups was significantly lower （P〈0.05） than that in the control group p[（11.32±1.50）/HP]. Conclusions The significant inhibiory effect of TNP-470 on the growth of human glioblastoma U-251 xenografts is similar to that of BCNU in the nude mice.