修饰的反义寡脱氧核苷酸对胰腺癌细胞生长和靶基因表达的抑…

观察修饰过的反义寡脱氧核苷酸对人胰腺癌细胞生长和靶基因表达的抑制作用。

Inhibition of cell growth and target gene expression of human pancreatic carcinoma cells by modified antisense oligodeoxynucleotide

OBJECTIVE: To investigate the inhibitory effects of modified antisense oligodeoxynucleotide on cell growth, 3H-TdR incorporation rate and target gene expressions of human pancreatic carcinoma cells as a comparison with the effectiveness of nonmodified antisense oligodeoxynucleotide (ASODN) resported previously. METHODS: Synthesized modified antigsense oligodeoxynucleotides (antisense phosphorothioate oligodeoxynucleotides, ASPODN) complementary to the cap regions of c-myc and Ki-ras genes were used to treat PC-2 and PC-3 human pancreatic carcinoma cell line cells with multiple small (10 micrograms) doses or one single dose (15 micrograms). After treatment, cell growth rates and 3H-TdR incorporation rates were estimated, and the concurrent oncogene expressions were studied by adopting RT-PCR technique. RESULTS: After multiple ASPODN exposures, the cell growth rates and 3H-TdR incorporation rates were significantly inhibited, the inhibition was maintained for more than two weeks. On the 14th day, the cell growth rates of the ASPODN groups were reduced to 38%-43% of that of the controls, and the 3H-TdR incorporation rates were 18%-33% of that of the controls, there were also marked inhibition or down-regulation of target genes (c-myc and Ki-ras) expressions. After the 15 micrograms single dose treatment, the inhibition of cell growth, 3H-TdR incorporation and target gene expressions lasted for 4 days. CONCLUSIONS: The results of this study confirm the fact that ASPODN exerts a more strong inhibitory effect on pancreatic carcinoma cells than the non-modified ASODN.