Influence of insulin-like growth factor II antisense oligonucleotides on growth of hepatoma cell lines

Autor: Huang, Shi Xin, 黃世心
Rok vydání: 1995
Druh dokumentu: 學位論文 ; thesis
Popis: 83
Insulin-like growth factor II (IGF-II) is a single chain poly- peptide growth factor which is structurally related to insulin and insulin-like growth factor type I (IGF-I).IGF-II is thought to be involved in fetal tissues development and growth. Many papers have showed that the expression of IGF-II mRNA is markedly elevated in several human fetal and tumor tissues. It is suggested that the growth factor might be involved in cancer progression by an autocrine/ paracrine mechanism. The main purpose of the present study was to characterize the role of IGF-II in hepatoma cell lines growth. We set up an enzyme immunoassay system to determinate the IGF-II protein levels of several hepatoma cell lines and added IGF-II to cell culture system to see the mitogenic effect of IGF-II. We also constructed a vector which contained IGF-II cDNA and SP6 / T7 promoters, then synthesized antisense oligonucleotides which are complementary to IGF-II mRNA. We applied antisense oligo- nucleotides in this in vitro transcription/ translation system. After screening useful antisense oligonucleotides in vitro, we utilized cell culture system to inhibit IGF-II production and evaluated cell growth rate to find the relationship between IGF-II and cell growth. Finally, we subcutaneously injected HepG2 cells and antisense oligonucleotides to SCID mice and observed tumorigenesis progression whether it could be delayed by inject-ing antisense oligonucleotides. We found that antisense oligonucleotides can inhibit IGF-II production. Cell growth rate would slow down when IGF-II pro- duction was inhibited by antisense oligonucleotides. This finding suggested that IGF-II could be an autocrine/ paracrine growth factor of hepatoma HepG2 cells.
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