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Titolo:
In vitro and in vivo suppression of growth of rat liver epithelial tumor cells by antisense oligonucleotide against protein kinase C-alpha
Autore:
Lin, SB; Wu, LC; Huang, SL; Hsu, HL; Hsieh, SH; Chi, CW; Au, LC;
Indirizzi:
Vet Gen Hosp, Dept Med Res, Taipei 11217, Taiwan Vet Gen Hosp Taipei Taiwan 11217 osp, Dept Med Res, Taipei 11217, Taiwan Natl Taiwan Univ, Natl Taiwan Univ Hosp, Coll Med, Sch Med Technol, Taipei, Taiwan Natl Taiwan Univ Taipei Taiwan oll Med, Sch Med Technol, Taipei, Taiwan Natl Taiwan Univ, Natl Taiwan Univ Hosp, Coll Med, Dept Lab Med, Taipei, Taiwan Natl Taiwan Univ Taipei Taiwan , Coll Med, Dept Lab Med, Taipei, Taiwan
Titolo Testata:
JOURNAL OF HEPATOLOGY
fascicolo: 4, volume: 33, anno: 2000,
pagine: 601 - 608
SICI:
0168-8278(200010)33:4<601:IVAIVS>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
NF-KAPPA-B; OXIDE SYNTHASE EXPRESSION; PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDE; INHIBITION; CANCER; TUMORIGENICITY; RECEPTORS; DEATH; MICROENVIRONMENT; OVEREXPRESSION;
Keywords:
antisense oligonucleotide; apoptosis; liver stem-like tumor cell; orthotopic tumor model; protein kinase C-alpha;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
49
Recensione:
Indirizzi per estratti:
Indirizzo: Au, LC Vet Gen Hosp, Dept Med Res, Taipei 11217, Taiwan Vet Gen Hosp Taipei Taiwan 11217 pt Med Res, Taipei 11217, Taiwan
Citazione:
S.B. Lin et al., "In vitro and in vivo suppression of growth of rat liver epithelial tumor cells by antisense oligonucleotide against protein kinase C-alpha", J HEPATOL, 33(4), 2000, pp. 601-608

Abstract

Background/Aims: It has been hypothesized that liver stem cells may be activated and proliferate upon liver injury and may participate in the development of liver cancer. GP7TB, a rat liver epithelial tumor cell line, possesses characteristics of liver stem-like cells and can develop into a tumor in syngeneic Fischer 344 rat. We found that protein kinase C-alpha (PKC-alpha) is overexpressed in GP7TB cells. The importance of PKC-alpha for this liver tumor cell was elucidated. Methods: Antisense oligonucleotide (ODN) was applied to suppress the production of PKC-alpha in GP7TB cells in vitro and in vivo. Cell viability was measured by acid phosphatase assay. The cellular levels of PKC-alpha and Bcl-2 were monitored by Western-blot analysis. Activation of nuclear factor NF-kappa B was analyzed by electrophoretic mobility shift assay. Cell cycle phase distribution was monitored by FACScan. Cell apoptosis was detected byTUNEL assay and histochemical staining of tumor tissue sections. The in vivo experiment was conducted by implanting tumor mass of GP7TB in the liver of F-344 rat and continuous delivery of the ODN by a mini-osmotic pump. Results: Antisense ODN effectively suppressed the level of PKC-alpha that resulted in the decrease of Bcl-2 and nuclear NF-kappa B. The cumulative viable cells also decreased dramatically for the antisense-treated group. FACScan showed that the cells were arrested at early S-phase. These cells in turn went into apoptosis without completing a cell cycle. It was found that growth of the tumor was suppressed efficiently by antisense ODN. Cell apoptosis was found in the orthotopic tumor. The normal liver cells were not affected. Conclusions: A lethal effect of depressing the level of PKC-alpha in GP7TBcells and success in suppressing orthotopic tumor growth in vivo suggests that PKC-alpha antisense ODN would be a promising therapeutic agent for some liver cancers.

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Documento generato il 20/09/20 alle ore 07:51:32