摘要
This study investigated the effect of TNP-470 in combination with carmustine (BCNU) on the growth of subcutaneously implanted human glioblastoma xenografts in nude mice.Human glioblastoma U-251 cells (1×10 7) were injected into 24 nude mice subcutaneously.The tumor-bearing mice were randomly divided into 4 groups on the seventh day following tumor implantation:TNP-470 group,in which TNP-470 was given 30 mg/kg subcutaneously every other day 7 times;BCNU group,in which 20 mg/kg BCNU were injected into peritoneal cavity per 4 days 3 times;TNP-470 plus BCNU group,in which TNP-470 and BCNU were coadministered in the same manner as in the TNP-470 group and the BCNU group;control group,in which the mice were given 0.2 mL of the mixture including 3% ethanol,5% acacia and 0.9% saline subcutaneously every other day 7 times.The tumor size and weights were measured.The tumor microvessel density (MVD) was determined by immunostaining by using goat-anti-mouse polyclonal antibody CD105.The results showed that on the 21th day following treatment,the volume of xenografts in the TNP-470 plus BCNU group was (108.93±17.63)mm 3,markedly lower than that in the TNP-470 group [(576.10±114.29)mm 3 ] and the BCNU group [(473.01±48.04)mm 3 ] (both P【0.01).And the xenograft volume in these 3 treatment groups was even much lower than that in the control group [(1512.61±470.25) mm 3 ] (all P【0.01).There was no significant difference in the volume of xenografts between the TNP-470 group and the BCNU group (P】0.05).The inhibition rate of the tumor growth in the TNP-470 plus BCNU group was (92.80±11.37)%,notably higher than that in the TNP-470 group [(61.91±6.29)%] and the BCNU group [(68.73±9.65)%] (both P【0.01) on the 21th day following treatment.There was no significant difference in the inhibition rate of tumor growth between the TNP-470 group and the BCNU group (P】0.05).The MVD of xenografts in the TNP-470 plus BCNU group was decreased significantly as compared with that in the TNP-470 group or the BCNU group (both P【0.05).The MVD of xenografts in the 3 treatment groups was markedly reduced as compared with that in the control group (all P【0.05).No significant changes in weights were observed before and after the treatment in each group (all P】0.05).It was concluded that the combination of TNP-470 and BCNU can significantly inhibit the growth of human glioblastoma xenografts in nude mice without evident side effects.
This study investigated the effect of TNP-470 in combination with carmustine (BCNU) on the growth of subcutaneously implanted human glioblastoma xenografts in nude mice.Human glioblastoma U-251 cells (1×10 7) were injected into 24 nude mice subcutaneously.The tumor-bearing mice were randomly divided into 4 groups on the seventh day following tumor implantation:TNP-470 group,in which TNP-470 was given 30 mg/kg subcutaneously every other day 7 times;BCNU group,in which 20 mg/kg BCNU were injected into peritoneal cavity per 4 days 3 times;TNP-470 plus BCNU group,in which TNP-470 and BCNU were coadministered in the same manner as in the TNP-470 group and the BCNU group;control group,in which the mice were given 0.2 mL of the mixture including 3% ethanol,5% acacia and 0.9% saline subcutaneously every other day 7 times.The tumor size and weights were measured.The tumor microvessel density (MVD) was determined by immunostaining by using goat-anti-mouse polyclonal antibody CD105.The results showed that on the 21th day following treatment,the volume of xenografts in the TNP-470 plus BCNU group was (108.93±17.63)mm 3,markedly lower than that in the TNP-470 group [(576.10±114.29)mm 3 ] and the BCNU group [(473.01±48.04)mm 3 ] (both P<0.01).And the xenograft volume in these 3 treatment groups was even much lower than that in the control group [(1512.61±470.25) mm 3 ] (all P<0.01).There was no significant difference in the volume of xenografts between the TNP-470 group and the BCNU group (P>0.05).The inhibition rate of the tumor growth in the TNP-470 plus BCNU group was (92.80±11.37)%,notably higher than that in the TNP-470 group [(61.91±6.29)%] and the BCNU group [(68.73±9.65)%] (both P<0.01) on the 21th day following treatment.There was no significant difference in the inhibition rate of tumor growth between the TNP-470 group and the BCNU group (P>0.05).The MVD of xenografts in the TNP-470 plus BCNU group was decreased significantly as compared with that in the TNP-470 group or the BCNU group (both P<0.05).The MVD of xenografts in the 3 treatment groups was markedly reduced as compared with that in the control group (all P<0.05).No significant changes in weights were observed before and after the treatment in each group (all P>0.05).It was concluded that the combination of TNP-470 and BCNU can significantly inhibit the growth of human glioblastoma xenografts in nude mice without evident side effects.
