TY - JOUR
T1 - Radiation-inducible TNF-α gene expression under stress-inducible promoter gadd 153 for cancer therapy
AU - Ito, Akira
AU - Shinkai, Masashige
AU - Hakamada, Kazumi
AU - Honda, Hiroyuki
AU - Kobayashi, Takeshi
N1 - Funding Information:
We are grateful to Prof. Nikki Holbrook (National Institute on Aging, Baltimore, MD, USA) for providing the JymCAT0 plasmid including the gadd 153 promoter, Dr. Hirohumi Hamada (Cancer Chemotherapy Center, Japanese Foundation for Cancer Research) for providing the plasmid SKhTNF-cz including the hTNF-a gene, Prof. Jun Yoshida (Medical School, Nagoya University) for pro-riding U251-SP cells, and Mr. Shigefumi Imai (Cobalt 60 y-Irradiation Laboratory, Nagoya University). This study was partially funded by a Grant-in-Aid for Scientific Research (No. 13218062 and 13853005) from the Ministry of Education, Culture, Sports and Technology of Japan.
PY - 2001
Y1 - 2001
N2 - We demonstrated the effectiveness of radiation-inducible expression of the TNF-α gene for cancer therapy in vitro. The TNF-α gene under the control of the stress-inducible promoter, gadd 153, was introduced into the human glioma cell line, U251-SP. Without cobalt-60 gamma irradiation, no cytotoxicity against the transfected cells was observed. When the transfected cells were irradiated with 10 or 20 gray (Gy), the gadd 153 promoter was highly induced and the expression level of TNF-α increased. Five days after the irradiation, the TNF-α productions of each cell irradiated with 10 and 20 Gy were 30 and 100 times higher than the basal level, respectively. The cytotoxicities against the transfected cells 5 d after irradiation with 10 and 20 Gy were 79% or 91%, respectively, which are much higher than those against the nontransfected cells that were irradiated at the same dose (43% and 78%, respectively). These results demonstrate that the gadd 153-TNF-α system may be an effective tool for radiosurgery of malignant brain tumors.
AB - We demonstrated the effectiveness of radiation-inducible expression of the TNF-α gene for cancer therapy in vitro. The TNF-α gene under the control of the stress-inducible promoter, gadd 153, was introduced into the human glioma cell line, U251-SP. Without cobalt-60 gamma irradiation, no cytotoxicity against the transfected cells was observed. When the transfected cells were irradiated with 10 or 20 gray (Gy), the gadd 153 promoter was highly induced and the expression level of TNF-α increased. Five days after the irradiation, the TNF-α productions of each cell irradiated with 10 and 20 Gy were 30 and 100 times higher than the basal level, respectively. The cytotoxicities against the transfected cells 5 d after irradiation with 10 and 20 Gy were 79% or 91%, respectively, which are much higher than those against the nontransfected cells that were irradiated at the same dose (43% and 78%, respectively). These results demonstrate that the gadd 153-TNF-α system may be an effective tool for radiosurgery of malignant brain tumors.
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U2 - 10.1016/S1389-1723(01)80324-8
DO - 10.1016/S1389-1723(01)80324-8
M3 - Article
C2 - 16233154
AN - SCOPUS:0035702260
SN - 1389-1723
VL - 92
SP - 598
EP - 601
JO - Journal of Bioscience and Bioengineering
JF - Journal of Bioscience and Bioengineering
IS - 6
ER -
