Document Detail

Increase of BCNU sensitivity by wt-p53 gene therapy in glioblastoma lines depends on the administration schedule.
MedLine Citation:
PMID:  10455409     Owner:  NLM     Status:  MEDLINE    
In this article, we investigated the effect induced by the reintroduction of wild-type p53 (wt-p53) protein on BCNU sensitivity in the ADF glioblastoma line. Using a wt-p53 recombinant adenovirus (Ad-p53), we demonstrated that exogenous wt-p53 expression was able to increase the sensitivity to BCNU in ADF cells. Interestingly, this effect was more evident when Ad-p53 infection was performed after BCNU treatment compared with the opposite sequence. To understand the biological basis of these different behaviors, we analyzed the cell cycle of the differently treated cells. We found that Ad-p53 infection induced a persistent accumulation of cells in the G0/G1 phase while, as expected, BCNU induced a block in the G2-M phase. Ad-p53-->BCNU sequence did not significantly modify the cell cycle profile in respect of Ad-p53 infected cells. In contrast, BCNU-->Ad-p53 sequence provoked G2-M arrest similar to that observed after treatment with BCNU alone, but prevented the later recovery of the cells through the cell cycle, by driving the cells to apoptotic death. These results demonstrate that the administration sequence is important to increase drug sensitivity. To generalize the phenomenon observed on ADF line, the antiproliferative effect of the two different schedules was analyzed on other glioblastoma lines (A172, CRS-A2, U373MG) with different BCNU sensitivity and p53 status. The data obtained confirm that the wt-p53 gene transfer enhances BCNU sensitivity in glioblastoma cells depending on the administration sequence.
A Biroccio; D D Bufalo; A Ricca; C D'Angelo; G D'Orazi; A Sacchi; S Soddu; G Zupi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Gene therapy     Volume:  6     ISSN:  0969-7128     ISO Abbreviation:  Gene Ther.     Publication Date:  1999 Jun 
Date Detail:
Created Date:  2000-02-24     Completed Date:  2000-02-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9421525     Medline TA:  Gene Ther     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1064-72     Citation Subset:  IM    
Experimental Chemotherapy Laboratory, Regina Elena Cancer Institute, Rome, Italy.
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MeSH Terms
Antineoplastic Agents, Alkylating / therapeutic use*
Brain Neoplasms / therapy*
Carmustine / therapeutic use*
Drug Administration Schedule
Drug Resistance, Neoplasm
Gene Therapy / methods*
Genes, p53 / genetics
Glioblastoma / therapy*
Tumor Cells, Cultured
Tumor Suppressor Protein p53 / genetics*
Reg. No./Substance:
0/Antineoplastic Agents, Alkylating; 0/Tumor Suppressor Protein p53; 154-93-8/Carmustine

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