Efficacy of bispecific targeted immunotoxin DTATEGF against NSCLC brain metastatic tumor PC9-BrM3 cells.
10.3969/j.issn.1672-7347.2013.12.003
- Author:
Jun HUANG
1
;
Bo LI
;
Jian LI
;
Dingyang LIU
;
Yan LI
;
Walter A HALL
;
Dun YUAN
Author Information
1. Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Antibodies, Bispecific;
pharmacology;
Apoptosis;
Brain Neoplasms;
drug therapy;
Carcinoma, Non-Small-Cell Lung;
drug therapy;
Cell Cycle;
Cell Line, Tumor;
Humans;
Immunotoxins;
pharmacology;
Mice;
Mice, Nude;
Neovascularization, Pathologic;
prevention & control;
Xenograft Model Antitumor Assays
- From:
Journal of Central South University(Medical Sciences)
2013;38(12):1217-1222
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the in vitro and in vivo anticancer efficacy of the immunotoxin DTATEGF against human NSCLC brain metastatic tumor PC9-BrM3 cell line.
METHODS:The effect of the immunotoxin DTATEGF was tested for its ability to inhibit the proliferation of PC9-BrM3 cells in vitro by MTT assay. The cell cycle and the apoptosis of cells with 1 pmol/L DTATEGF were examined by flow cytometry. In vivo, 2 μg of DTATEGF or control Bickel3 was given intratumor to nude mice with established PC9-BrM3 xenografts on their hips, and tumor volumes were measured and tumor samples were investigated by immunchistochemistry SABC method. The microvessel density (MVD) was measured in each group.
RESULTS:In vitro, DTATEGF killed PC9-BrM3 cells and showed an IC50 of 1 pmol/L. The apoptotic rate in the 1 pmol/L DTATEGF group was (64.0±0.5)% , significantly higher than that in the control group (1.5±0.4)% (P<0.01). The cell cycle was obviously inhibited by DTATEGF in a dose-dependent manner. The percentage of cells treated with 1 pmol/L DTATEGF in SubG0/G1 phase was (32.0±1.5)%, significantly higher than that in the control group (2.0±0.4)% (P<0.01). In vivo, DTATEGF significantly inhibited the growth of PC9-BrM3 hip tumors (P<0.05). The MVD of the DTATEGF group was (15.6±4.6)/mm2, significantly lower than that of the control group (31.2±5.4)/mm2 (P<0.01).
CONCLUSION:DTATEGF inhibits the growth of the PC9-BrM3 cell line and induces its apoptosis. It is highly efficacious against human metastatic NSCLC brain tumor and against neovascularization.
