烟曲霉醇与卡氮芥联合应用抑制U-251细胞异种移植瘤的研究

目的 观察烟曲酶醇(TNP-470)和卡氮芥(BCNU)联合应用对U-251胶质母细胞瘤细胞裸鼠皮下移植瘤生长的影响.方法 将U-251细胞株接种至裸鼠皮下,第7天荷瘤裸鼠随机分为TNP-470治疗组、BCNU治疗组、TNP-470和BCNU联合治疗组、对照组.测体质量、肿瘤体积、抑瘤率、肿瘤微血管密度(MVD).结果 (1)各组裸鼠体质量于治疗前后均无显著变化(P均>0.05).(2)治疗后第21天联合治疗组移植瘤体积[(108.93±17.63)mm~3]明显小于TNP-470治疗组[(576.10±114.29)mm~3]及BCNU治疗组[(473.01±48.04)mm~3](P均<0.01);各治疗组移植瘤体积均小于对照组[(1512.61±70.25)mm~3](P均<0.01);TNP-470治疗组与BCNU治疗组间移植瘤体积差异无统计学意义(P>0.05).(3)治疗后第21天联合治疗组的抑瘤率(92.80±11.37)%显著高于TNP-470治疗组(61.91±6.29)%和BCNU治疗组(68.73±9.65)%(P均<0.01),TNP-470治疗组与BCNU治疗组间抑瘤率差异无统计学意义(P>0.05).(4)联合治疗组移植瘤MVD[(4.23±0.83)个/视野]明显低于TNP-470治疗组[(5.70±0.85)个/视野]和BCNU治疗组[(8.60±0.87)个/视野](P均<0.05);TNP-470治疗组移植瘤MVD显著低于BCNU治疗组(P<0.05);各治疗组移植瘤MVD均较对照组[(11.32±1.50)个/视野]显著降低(P均<0.05).结论 TNP-470和BCNU联用对U-251胶质母细胞瘤细胞裸鼠皮下移植瘤的生长有显著抑制作用而无明显不良反应.

The effect of combination of TNP-470 and BCNU on growth of human glioblastoma U-251 xenografts

Objective To investigate the effect of combining TNP-470 and BCNU on growth of subcutaneously implanted human glioblastoma xenografts U-251 in nude mice. Methods 1×10~+7 of hu-man glioblastoma U-251 cells were injected simultaneously to 24 nude mice subcutaneously. The mice were randomly divided into 4 groups on the seventh day following tumor implantation. In TNP-470-treated group,TNP-470 was given 30 mg/kg subcutaneously every other day for 7 times. In BCNU-treated group, 20 mg/kg BCNU was injected into peritoneal cavity every 4 days for 3 times. In the group treated with TNP-470 combined with BCNU, both TNP-470 and BCNU were administered the same as in TNP-470-trea-ted group and BCNU-treated group. The control group was given 0.2 ml of the mixture including 3% etha-nol,5% acacia and 0.9% saline subcutaneously every other day for 7 times. The tumor size and weights were recorded. The tumor microvessel density (MVD) was measured by goat-anti-mouse polyclonal anti-body CD105 immunostaining. Results (1) No significant changes in weights were observed before and after the treatment in each group (all P>0.05). (2) On the 21st day following treatment,the volume of xenografts treated with TNP-470 combined with BCNU [(108.93±17.63) mm~3]was reduced markedly as compared with that in both the TNP-470-treated group [(576.10±114.29) mm~3]and the BCNU-trea-ted group [(473.01±48.04) mm~3](both P<0.01),and that in the above three groups was significant-ly decreased as compared with the control group [(1512.61±470.25) mm~3](all P<0.01). There was no significant difference in the volume of xenografts between TNP-470-treated group and BCNU-treated group (P>0.05). (3) The inhibition rate of tumor growth in the group treated with TNP-470 combined with BCNU [(92.80±11.37)%]was notably higher than that in the TNP-470-treated group [(61.91±6.29)%]or the BCNU-treated group [(68.73±9.65)%](both P<0.01) on the 21st day following treatment. There was no significant difference in the inhibition rate of tumor growth between TNP-470-treated groupand BCNU-treated group (P > 0.05). (4) The MVD of xenografts in the group treated with TNP-470 combined with BCNU (4.23±0.83) was decreased significantly as compared with that in the TNP-470-treated group (5.70±0.85) or the BCNU-treated group (8.60±0.87) (both P<0.05), and that in the a-bove three groups was reduced markedly as compared with that in the control group (11.32±1.50) (all P <0.05). The MVD of xenografts in TNP-470-treated group was significantly lower than that in BCNU-trea-ted group (P<0.05). Conclusion The combination of TNP-470 and BCNU could significantly inhibit the growth of human glioblastoma xenografts U-251 in nude mice without evident side effects.