Antisense Oligonucleotides Targeting Protein Kinase C- Cause Growth Inhibition and Apoptosis of Rat Hepatoma Cell Line GP7TB─in vitro and in vivo study
| Autor: | Siao-ling Huang, 黃小玲 |
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| Rok vydání: | 1999 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 87 Hepatocellular carcinoma is one of the world’s most common malignancies. It is still almost impossible to design well-controlled therapy. It has been found that protein kinase C play an important role in cell growth and proliferation. In this thesis, antisense oligonucleotide (ATON) designed for inhibiting translation of protein kinase C-(PKC-) found to cause growth inhibition and apoptosis of rat hepatoma cell line-GP7TB. Cell growth was 70% decreased after treatment of 10M ATON for 96 hr. The influence of the antisense oligonucleotides was compared with Go6976 and phorbol ester. All of them caused growth inhibition at an IC50= 4 M, 5 M and 3 M respectively. However the treatment with Go6976 did not effect protein level of PKC- Shorter versions of the antisense, namely from the 20mer prototype to 18mer, 16mer or 14mer were still effective. Inhibition of PKC- protein synthesis was studied by Western blotting analysis and PKC activity assay. Most pronounced decrease in protein level was observed 60 hr after the treatment of ATON. While activity of classical PKC was inhibited >90%. Cell cycle analysis by flow cytometer indicated that the ATON caused a late S-phase arrest and subsequently apoptosis of the cells. In animal model, the rat treated with m antisense showed a 60% decrease in tumor volume. This finding suggested that PKC-may play an important role in regulating cell apoptosis in GP7TB cells. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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