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Inhibition of hepatocellular carcinoma growth by antisense oligonucleotides to type I insulin-like growth factor receptor in vitro and in an orthotopic model

, : Inhibition of hepatocellular carcinoma growth by antisense oligonucleotides to type I insulin-like growth factor receptor in vitro and in an orthotopic model. Hepatology Research 37(5): 366-375

Aim: The type I insulin-like growth factor receptor (IGF-IR) is overexpressed in many tumors including human hepatocellular carcinoma (HCC). It is a critical signaling molecule for tumor cell proliferation and survival. In the present study, IGF-IR expression was down-regulated by phosphorothioate antisense oligonucleotides (AS[S]ODN) to evaluate their specific effects on growth of hepatoma cells in vitro and in vivo.Methods: HepG2 cells were transfected with different doses of AS[S]ODN, sense [S]ODN, mismatch [S]ODN, or Lipofectin for 72 h, and cell proliferation was analyzed by MTS assay. In vivo, an orthotopic transplant model of HCC was established in nude mice, which were then injected with AS[S]ODN, sense [S]ODN, 5-fluorouracil or saline. At the endpoint of treatment, the tumors were excised and evaluated.Results: Compared to sense and mismatched oligonucleotides, AS[S]ODN targeting to IGF-IR mRNA significantly inhibited hepatoma cell lines HepG2 proliferation and IGF-IR expression at both mRNA and protein levels. The in vivo results showed that systemic treatment also resulted in significant inhibition in tumor growth. Tumor growth in mice treated with AS[S]ODN (50 and 75 mg/kg per day) was significantly inhibited (71.81% and 61.74%, respectively) compared to the saline-treated group (P < 0.01) in a dose-dependent manner. The antitumor effect of IGF-IR AS[S]ODN was associated with down-regulation of IGF-IR in tumor xenografts. Furthermore, IGF-IR AS[S]ODN prevented liver recurrence tumor growth and metastasis in the lung, showing a dose-dependent response. The level of serum alpha-fetoprotein in AS[S]ODN-treated groups was also decreased in a dose-dependent manner, and a good correlation was observed between tumor volume and serum alpha-fetoprotein concentration.Conclusions: These data suggest that IGF-IR AS[S]ODN can effectively and specifically inhibit HCC growth in vitro and in vivo. Blockage of IGF-IR expression could be a promising therapeutic approach for the management of patients with HCC.


PMID: 17441810

DOI: 10.1111/j.1872-034X.2007.00055.x

Other references

Weber, J.T.; O'Connor, M.F.; Hayataka, K.; Colson, N.; Medora, R.; Russo, E.B.; Parker, K.K., 1997: Activity of Parthenolide at 5HT2A receptors. Parthenolide, a sesquiterpene lactone and putative active principle of Tanacetum parthenium, displaced [superscript 3H]ketanserin from 5HT2A receptors (isolated from rat and rabbit brains) and cloned 5HT2A receptors with Ki values of 100-250 micro...

Bandurska, Hanna, 1998: Implication of ABA and proline on cell membrane injury of water deficit stressed barley seedlings. The aim of this work was to examine the ability of ABA and proline to counteract the deleterious effect of water deficit stress on cell membrane injuries. Six-day-old seedlings of two barley genotypes (cv. Aramir, line R567) were treated with ABA...

Kirsch, I.; Milling, L.S.; Burgess, C., 2000: Suggestion difficulty as a hypothesized moderator of the relation between absorption and suggestibility: A new spectral analysis. Measures of hypnotic suggestibility and absorption were administered to 146 participants in the guise of different experiments. A spectral analysis was performed by correlating the difficulty of individual hypnotic suggestions with the magnitude o...

Abney, T.; Richards, T., 1978: Influence of Cercospora kikuchii conidial concentration of purple seed strain of Glycine max (L.) Merr. Phytopathology news 12 (9) 204

Brousse P., 1982: Volcanic apparatuses of the Central Massif. Documents - BR

Américo, M.F.; Oliveira, R.B.; Corá, L.A.; Marques, R.G.; Romeiro, F.G.; Andreis, U.; Miranda, Jé.Ricardo.A., 2010: The ACB technique: a biomagentic tool for monitoring gastrointestinal contraction directly from smooth muscle in dogs. The aim of this paper was to verify whether AC biosusceptometry (ACB) is suitable for monitoring gastrointestinal (GI) contraction directly from smooth muscle in dogs, comparing with electrical recordings simultaneously. All experiments were perfo...

Tanaka, T.; Takahashi, K.; Morita, H.; Uchida, Y.; Nagase, K.; Hayashi, H.; Yamatogi, Y.; Kitamura, I.; Kimoto, H., 1984: Chronic granulomatous disease of childhood and sea-blue histiocytosis. A pathologic study of an autopsy case. A boy, who started remittent fever reaching 40 degrees C at the age of 4 years and 9 months and gradually developed hepatosplenomegaly, lymphadenopathy, pancytopenia, and hypergammaglobulinemia, is reported. Aspirated bone marrows contained sea-bl...

Dorsch, M.; Calder, I.; Roder, D.; Esterman, A., 1984: Birth defects and the consumption of nitrates in food and water in the Lower South-East of South Australia: An exploratory study. Nitrate levels in 136 samples of 5 commonly consumed vegetables grown in areas of South Australia where groundwater generally had high nitrate levels were examined to test the hypothesis that food grown in this area would have markedly elevated ni...

Jasmin, C.; Joffe, F.S.; Klein, B.; Kerdiles-LeBousse, C., 1976: Physiopathology of human and virus-induced murine leukemias. The authors describe a coherent model for differentiated leukemias derived from physiopathological studies on Friend leukemia. In Friend leukemia, Friend virus induces permanent differentiation of erythropoietin-responsive cells. This erythropoiet...

Cocke, J.; Jr., 1977: Fluorescent insect growth regulators (HGR): their effects on Aedes aegypti (L. ) (Diptera: Culicidae); and potential use in studying insect hormone and growth regulator action. Dissertation Abstracts lnternational, 3712: 5957