Overcoming of radioresistance in human gliomas by p21WAF1/CIP1 antisense oligonucleotide.
Malignant gliomas are highly resistant tumors against gamma-irradiation and contained overexpression of p21WAF1/CIP1 (p21). Overexpression of p21 enhanced clonogenic survival and suppressed apoptosis after gamma-irradiation in human brain tumor cell lines with or without p53 protein deficiency. The effect of antisense oligonucleotide to p21 against the gamma-irradiation-induced apoptosis and cytotoxicity in malignant glioma cell lines was examined. Antennapedia homeodomain internalization peptide was used as an insertion vector. The high transfection efficiency of Antennapedia homeodomain internalization peptide joined with antisense oligonucleotide was observed. The pretreatment with antisense oligonucleotide enhanced the gamma-irradiation-induced apoptosis and cytotoxicity in radioresistant glioma cells. p21 may represent an important new target for radiosensitization protocols, possibly involving antisense oligonucleotide directed against p21.
Kokunai
T
T
Department of Neurosurgery, Kakogawa Municipal Hospital, Japan.
Urui
S
S
Tomita
H
H
Tamaki
N
N
D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001483:Base Sequence; D001932:Brain Neoplasms; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D051357:Cyclin-Dependent Kinase 2; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000032:analysis / Q000235:genetics*; D004791:Enzyme Inhibitors; D005720:Gamma Rays; D005910:Glioma; D006801:Humans; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011836:Radiation Tolerance / Q000187:drug effects / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases