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Titolo:
Increase of BCNU sensitivity by wt-p53 gene therapy in glioblastoma lines depends on the administration schedule
Autore:
Biroccio, A; Del Bufalo, D; Ricca, A; DAngelo, C; DOrazi, G; Sacchi, A; Soddu, S; Zupi, G;
Indirizzi:
Regina Elena Inst Canc Res, Expt Chemotherapy Lab, I-00158 Rome, Italy Regina Elena Inst Canc Res Rome Italy I-00158 y Lab, I-00158 Rome, Italy Regina Elena Inst Canc Res, Mol Oncogenesis Lab, I-00158 Rome, Italy Regina Elena Inst Canc Res Rome Italy I-00158 s Lab, I-00158 Rome, Italy Univ G DAnnunzio, Dept Oncol & Neurosci, Chieti, Italy Univ G DAnnunzio Chieti Italy zio, Dept Oncol & Neurosci, Chieti, Italy
Titolo Testata:
GENE THERAPY
fascicolo: 6, volume: 6, anno: 1999,
pagine: 1064 - 1072
SICI:
0969-7128(199906)6:6<1064:IOBSBW>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
WILD-TYPE P53; TUMOR-SUPPRESSOR GENE; MALIGNANT GLIOMAS; CELL-CYCLE; IN-VITRO; INDUCED APOPTOSIS; MAMMALIAN-CELLS; DNA-DAMAGE; MUTATIONS; ADENOVIRUS;
Keywords:
BCNU; wt-p53; gene therapy; glioblastoma;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Zupi, G Regina-00158 Inst Canc Res, Expt Chemotherapy Lab, CRS Via Messi Oro 156, I Regina Elena Inst Canc Res CRS Via Messi Oro 156 Rome Italy I-00158
Citazione:
A. Biroccio et al., "Increase of BCNU sensitivity by wt-p53 gene therapy in glioblastoma lines depends on the administration schedule", GENE THER, 6(6), 1999, pp. 1064-1072

Abstract

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 BCNUin 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 thelater 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) withdifferent 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.

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Documento generato il 24/11/20 alle ore 14:41:02