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

Abstract

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 0.05). (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 0.05). (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. Key words: Glioma; Angiogenesis; BCNU