| The effect of YB-1 antisense oligonucleotides on tumor cell growth |
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Myung Sung Kim, Wan Sik Lee, Chang Hwan Park, Young Eun Joo, Hyun Soo Kim, Sung Kyu Choi, Jong Sun Rew, Young Do Jung, Sei Jong Kim, Bong Whan Ahn, Boo Ahn Shin |
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고려대학교 의과대학 내과학교실 |
| 원저:암세포 증식에 대한 YB-1 안티센스 올리고핵산염의 영향 |
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김명성, Wan Sik Lee, Chang Hwan Park, Young Eun Joo, Hyun Soo Kim, Sung Kyu Choi, Jong Sun Rew, Young Do Jung, Sei Jong Kim, Bong Whan Ahn, Boo Ahn Shin |
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| Abstract |
Background : Human YB-1 is a transcription factor that binds to the inverted CCAAT box in
the promoter region of a variety of genes such as PCNA, DNA polymerase and MDR. In this study
we evaluated the effect of YB-1 antisense oligonucleotides on tumor cell growth.
Methods
: Chang liver, HepG2 and CT-26 cells were cultured as immortalized cell lines. The
MTT (3-[4,5 -dimethylthiazol-2-yl] 2,5-diphenyltetrazolium bromide) assay, Northern blot and flow
cytometric analyses were used to determine cell growth, gene expression and cell cycle changes. In
an animal model, CT-26 cells were injected into Balb/c mice to induce tumor; YB-1 antisense
oligonucleotides were injected into the tail vein or tumor tissue of the mice; change of tumor size was
then measured.
Results
: Phosphorothioated YB-1 antisense oligonucleotides suppressed the proliferation of the
immortalized liver cells (Chang liver cells) and a variety of cancer cells (HepG2 and CT-26 cells);
however, it did not inhibit normal cell growth. The DOTAP/antisense oligonucleotide mixture showed
stronger effects on cell proliferation than did the antisense oligonucleotide alone. The YB-1 antisense
oligonucleotide decreased specific expression of the YB-1 mRNA in the immortalized cancer cell
lines. Flow cytometric analysis revealed that the inhibition of cell proliferation might have been due
to a decrease in the S phase of the cell cycle. We found that in an animal tumor model, the
administration of the YB-1 antisense oligonucleotide, in the vein or tumor tissues, decreased the
tumor size significantly.
Conclusions
: These results suggest that the YB-1 antisense oligonucleotide may inhibit growth
of a variety of cancer cells.(Korean J Med 71:293-301, 2006)
Key Words : YB-1, Antisense oligonucleotides, Tumor, Cell growth |
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