Efficacy of antiangiogenic targeted immunotoxin DTAT and DTATEGF against glioblastoma multiforme.
OBJECTIVE
To investigate the in vitro and in vivo anticancer efficacy of the immunotoxin DTAT and DTATEGF against globlastoma multiforme.


METHODS
The in vitro cytotoxicity of DTAT and DTATEGF was measured using MTT assay. In vivo studies were performed in which 18 nude mice were randomly divided into 3 groups and the glioma xenograft intracranial mouse model was constructed with U87-luc cell line of human glioma. Then 1 μg of DTAT, or DTATEGF, or a control protein Bickel3 was delivered intracranially by convection-enhanced delivery (CED) via an osmotic minipump. The brain tumor fluorescence signal intensity was investigated by bioluminescent imaging (BLI). Microvessel density (MVD) was measured by immunchistochemistry SABC method in each group.


RESULTS
In vitro DTAT and DTATEGF were found highly potent against U87-luc cell line, with IC(50) <0.01 nmol/L and IC(50)<1 nmol/L, respectively. In vivo BLI monitoring of the control group showed progressively increasing luminescence, while in the two treatment groups, luminescence was reduced on day 8, and increased slowly (P<0.05). The MVD of DTAT (31.6±5.2)/mm(2) and DTATEGF (25.1±6.5)/mm(2) groups had significant difference with that of the control group (51.3±7.4) /mm(2) (P<0.01).


CONCLUSIONS
Both DTAT and DTATEGF have potential in clinical application against globlastoma multiforme because of their ability to target the tumor cells and neovasculature simultaneously.
Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha 410008, China.
Jun
J
Huang
Dun
D
Yuan
Dingyang
D
Liu
Jian
J
Li
Yan
Y
Li
Walter
W
A Hall
Bo
B
Li
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D005909:Glioblastoma / Q000188:drug therapy*; D005910:Glioma; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D000922:Immunotoxins