Inhibitory effects of TNP-470 in combination with BCNU on tumor growth of human glioblastoma xenografts.
10.1007/s11596-010-0653-8
- Author:
Dongxiao YAO
1
;
Hongyang ZHAO
;
Fangcheng ZHANG
;
Jian CHEN
;
Xiaobing JIANG
;
Xianli ZHU
Author Information
1. Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. yaodongxiao@163.com
- Publication Type:Journal Article
- MeSH:
Angiogenesis Inhibitors;
administration & dosage;
Animals;
Antibiotics, Antineoplastic;
administration & dosage;
Antineoplastic Agents, Alkylating;
administration & dosage;
Antineoplastic Combined Chemotherapy Protocols;
therapeutic use;
Brain Neoplasms;
drug therapy;
Carmustine;
administration & dosage;
Cell Line, Tumor;
Cyclohexanes;
administration & dosage;
Female;
Glioblastoma;
drug therapy;
Humans;
Mice;
Mice, Inbred BALB C;
Mice, Nude;
Sesquiterpenes;
administration & dosage;
Xenograft Model Antitumor Assays
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2010;30(6):757-761
- CountryChina
- Language:English
-
Abstract:
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.
