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Titolo:
Induction of growth inhibition and apoptosis in pancreatic cancer cells byauristatin-PE and gemcitabine
Autore:
Li, YW; Singh, B; Ali, N; Sarkar, FH;
Indirizzi:
Wayne01tate Univ, Sch Med, Dept Pathol, Karmanos Canc Inst, Detroit, MI 482 Wayne State Univ Detroit MI USA 48201 Karmanos Canc Inst, Detroit, MI 482
Titolo Testata:
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
fascicolo: 6, volume: 3, anno: 1999,
pagine: 647 - 653
SICI:
1107-3756(199906)3:6<647:IOGIAA>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
POTENTIAL APPLICATION; SOLID TUMORS; LUNG-CANCER; BCL-XL; P21; DOLASTATIN-10; LEUKEMIA; KINASES; AGENTS; CYCLE;
Keywords:
apoptosis; auristatin-PE; gemcitabine; pancreatic cancer;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Sarkar, FH Wayne,540te Univ, Sch Med, Dept Pathol, Karmanos Canc Inst, 9374 Scott Hall Wayne State Univ 9374 Scott Hall,540 E Canfield Ave Detroit MIUSA 48201
Citazione:
Y.W. Li et al., "Induction of growth inhibition and apoptosis in pancreatic cancer cells byauristatin-PE and gemcitabine", INT J MOL M, 3(6), 1999, pp. 647-653

Abstract

Pancreatic adenocarcinoma. is the fifth leading cause of cancer related deaths in the United States. Treatment for this disease has largely been unsuccessful, which may partly be due to insufficient data regarding the molecular mechanisms of chemotherapeutic drugs currently being used as single agents or in combined modality regimens. In this study, we investigated the molecular mechanisms by which auristatin-PE, a newly developed experimental agent, and gemcitabine, a commercially available anti-cancer agent, exert their inhibitory effects on pancreatic cancer cell lines containing wild-typep53 (HPAC) and mutant p53 (PANC-1). Our results showed that auristatin-PE and gemcitabine inhibited cell growth and induced cell cycle arrest in G(2)/M and S phase, respectively. Auristatin-PE also induced apoptosis in both cell lines. Western blot analysis showed that auristatin-PE up-regulated the expression of wt-p53, p21(WAF1) and Bax, and down-regulated Bcl-2 and cyclin B in HPAC cells, while only up-regulation of p21(WAF1) and Bax was observed in PANC-1 cells. These results suggest that auristatin-PE may induce apoptosis and p21(WAF1) expression through p53-dependent or independent pathways, and that up-regulation of p21(WAF1) and Bax and down-regulation of Bcl-2 may be the molecular mechanism through which auristatin-PE inhibits cell growth and induces apoptosis. Furthermore, the up-regulation of p21(WAF1)and down-regulation of cyclin B may contribute to the G(2)/M cell cycle arrest. Combination of auristatin-PE and gemcitabine showed significantly greater inhibition of cell growth and up-regulated expression of p21(WAF1) andBax. From these results, we conclude that the selection of therapeutic agents based on their molecular mechanism may improve therapeutic outcome, andthat auristatin-PE may be more effective in the treatment of pancreatic cancer when given in combination with gemcitabine, rather than as a single agent.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/11/20 alle ore 10:56:18