[Targeted therapy of malignant glioma by a chimeric fusion toxin composed of IL-13 and Pseudomonas exotoxin in vitro].
OBJECTIVE
To examine the antitumor activity of IL-13PE38 on solid malignant glioma cells in vitro and to investigate its relationship between the antitumor activity of IL-13PE38 and the expression level of IL-13Rα2 in malignant glioma.


METHODS
Ten fresh tissues of anaplastic glioma and 11 fresh tissues of glioblastoma multiforme were obtained during craniotomy at First Affiliated Hospital, Wenzhou Medical College between June 2009 and December 2010. All fresh glioma cells were cultured in vitro with IL-13PE38. Then the cytotoxicity of IL-13PE38 was determined by colorimetric MTS proliferation assay and the SR (survival rate) calculated. The expression level of IL-13Rα2 was studied by immunohistochemical SABC method in 21 cases of malignant glioma. And the value of integrated optical density (IOD) was examined by computer assisted pathological image analysis system. The correlation between the IOD of IL-13Rα2 and the SR of malignant glioma cells was also studied.


RESULTS
(1) There were strongly positive expression of IL-13Rα2 in most cases (19/21, 90%). And the expression level of IL-13Rα2 in glioblastoma multiforme was higher than the expression level of IL-13Rα2 in anaplastic glioma (P < 0.05). (2) As the fresh malignant glioma cells were cultured with IL-13PE38 of same concentration, the number of surviving cells decreased in different degrees. The survival rate of 14 cases were < 70% and 9 cases < 50%. And the survival rate of anaplastic glioma cells was higher than that of glioblastoma multiforme cells (P < 0.05). (3) The IOD of IL-13Rα2 and the SR of malignant glioma cells were strongly negatively correlated (r = -0.093, P < 0.01).


CONCLUSIONS
A low concentration of IL-13PE38 shows a high level of cytotoxicity for solid malignant glioma cells. And its cytotoxic efficiency depends on the expression level of IL-13Rα2.
Department of Neurosurgery, Second Affiliated Hospital, Jianghan University, Wuhan 430050, China.
Jian-jian
JJ
Zhang
Rui-guang
RG
Weng
Jun
J
Liu
Han-ping
HP
Chen
Jun
J
Liu
Hui
H
Ye
Wei-ming
WM
Zheng
D000328:Adult; D000368:Aged; D001427:Bacterial Toxins / Q000627:therapeutic use*; D005098:Exotoxins / Q000627:therapeutic use*; D005260:Female; D005910:Glioma / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006801:Humans; D018793:Interleukin-13 / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011549:Pseudomonas; D053660:Receptors, Interleukin-13 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D001427:Bacterial Toxins; D005098:Exotoxins; D018793:Interleukin-13; D053660:Receptors, Interleukin-13; D011993:Recombinant Fusion Proteins