Abstract
Previous studies have shown that the negative cell cycle regulator WAP/Cip1 is often overexpressed in human gliomas and that WAF1/Cip1 overexpression may be a factor in cancer chemoresistance. We established a doxycycline-inducible WAP/Cip1 expression system in two glioblastoma cell lines and examined the role of WAF1/Cip1 in their response to the chemotherapy agents 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and cis- diamminedichloroplatinum (cisplatin), in an isogeneic background. Our results showed that the induction of WAF1/Cip1 expression rendered glioma cells resistant to cell death induced by BCNU and cisplatin. Using an in vivo host- cell reactivation DNA repair assay, we demonstrated that WAP/Cip1 enhances the repair of BCNU-induced DNA damage. We conclude that WAP/Cip1 allows repair of BCNU- and cisplatin-damaged DNA and protects glioma cells from chemotherapy agent-induced apoptosis. Thus, blocking WAF1/Cip1 production or function may serve as a useful chemosensitization regimen for glioma.
Original language | English (US) |
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Pages (from-to) | 1538-1543 |
Number of pages | 6 |
Journal | Cancer Research |
Volume | 58 |
Issue number | 7 |
State | Published - Apr 1 1998 |
ASJC Scopus subject areas
- Oncology
- Cancer Research