| Summary: | 碩士 === 國立臺灣大學 === 醫事技術學系研究所 === 86 === Hepatoma is the most popular cancer in Taiwan. One of new
ideas of treating cancer is to block the over-growth of the
proliferating cells. It has been found that protein kinase C α
(PKC-α) plays an important role in the signal transduction pathway.
The inhibition of PKC-α expression may block overgrowth of hepatome
cells.
Antisense oligonucleotides, which are able to hybridize to
complementary sequecnes and to inhibit the expression of target
sequence, is suitable for in vivo usage and promise as therapeutic
agents for viral infection or cancer. In the thesis, the influence
of the antisense oligonucleotides, unmodified or phosphorothioate-
modified, against PKC-α mRNA was studies in rat hepatomcecell-line
GP7TB.
Based on the results of stability of antisense oligonucleotides,
cell growth inhibition, cell cycle analysis, Western blotting, and
PKC-α kinase activity assay, we could conclude that (1) antisense
oligonucleotides αm can significantly inhibit the growth of GP7TB;
(2) unmodified antisense oligonucleotides are more effective than
that of phosphorothioates in the growth of inhibition GP7TB; (3)αm
causes apoptosis of GP7TB cells by S-phase arrest; (4) PKC-α may
play an important role in the growth of GP7TB. In addition, an animal
model was successfully set up by subcutaneously innoculating GP7TB on
Fischer 344 rat. Therefore, antisense oligoncueltides αm will be
employed in the rat model to further study the regulation of hepatoma
in vivo.
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