Overcoming of radioresistance in human gliomas by p21(WAF1/CIP1) antisenseoligonucleotide

Malignant gliomas are highly resistant tumors against gamma -irradiation an d contained overexpression of p21(WAF1/CIP1) (p21). Overexpression of p21 e nhanced clonogenic survival and suppressed apoptosis after gamma -irradiati on in human brain tumor cell lines with or without p53 protein deficiency. The effect of antisense oligonucleotide to p21 against the gamma -irradiati on-induced apoptosis and cytotoxicity in malignant glioma cell lines was ex amined. Antennapedia homeodomain internalization peptide was used as an ins ertion vector. The high transfection efficiency of Antennapedia homeodomain internalization peptide joined with antisense oligonucleotide was observed . The pretreatment with antisense oligonucleotide enhanced the gamma -irrad iation-induced apoptosis and cytotoxicity in radioresistant glioma cells. p 21 may represent an important new target for radiosensitization protocols, possibly involving antisense oligonucleotide directed against p21.