Basic-liver, pancreas, and biliary tractAcyclic retinoid inhibits human hepatoma cell growth by suppressing fibroblast growth factor-mediated signaling pathways
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Cell lines
Human liver tumor cell lines (HepG2, HLF, and HuH7) were obtained from the Riken cell bank (Tsukuba Science City, Japan). These cell lines were maintained in Dulbecco’s modified Eagle medium (GIBCO BRL, Gaithersburg, MD) supplemented with 10% heat-inactivated fetal bovine serum in an atmosphere containing 5% CO2.
Cell growth assays
To examine the effect of ACR on cell growth, 5 × 104 cells/well were seeded onto 6-well plates. The medium was changed the next day, and 0, 15, 30, 45, 60, or 90 μmol/L ACR (NIK-333;
ACR reduces the growth of human hepatoma cells
Because Muto et al had reported that an ACR prevented the occurrence of second primary tumors in patients with HCC,9 we evaluated the function of ACR on liver tumor cell growth in vitro. ACR exerted a dose-dependent inhibition of the growth of HLF, HuH7, and HepG2 human hepatoma cell lines, with median inhibitory concentrations of 10 μmol/L, 45 μmol/L, and 45 μmol/L, respectively (Figure 1 and data not shown), which were consistent with a previous report.10 The growth inhibitory effect was not
Discussion
ACR is the object of increasing interest because it has been shown to prevent the recurrence of human HCC after treatment of primary tumors.35 However, the underlying mechanisms of the clinical effects have not been fully elucidated. In this study, we found that ACR inhibits FGF receptor 3 expression, Rho activity, and SRF-mediated transcription, resulting in the inhibition of tumor cell growth. Conversely, these effects were completely neutralized by the overexpression of activated FGF
References (48)
- et al.
Malignant transformation of melanocytes to melanoma by constitutive activation of mitogen-activated protein kinase kinase (MAPKK) signaling
J Biol Chem
(2003) - et al.
Regulation of the fibroblast growth factor receptor 3 promoter and intron I enhancer by Sp1 family transcription factors
J Biol Chem
(1998) - et al.
c-fos induction by heat, arsenite, and cadmium is mediated by a heat shock element in its promoter
Biochem Biophys Res Commun
(1999) - et al.
Activation of intracellular signaling by hepatitis B and C virusesC-viral core is the most potent signal inducer
Hepatology
(2000) - et al.
Expression profiling of liver cell lines expressing entire or parts of hepatitis C virus open reading frame
Hepatology
(2002) - et al.
Interaction of transcription factors with serum response factor. Identification of the Elk-1 binding surface
J Biol Chem
(1998) - et al.
Growth hormone regulates ternary complex factors and serum response factor associated with the c-fos serum response element
J Biol Chem
(1997) - et al.
The Rho family GTPases RhoA, Rac1, and CDC42Hs regulate transcriptional activation by SRF
Cell
(1995) - et al.
Signal-regulated activation of serum response factor is mediated by changes in actin dynamics
Cell
(1999) - et al.
Receptor specificity of the fibroblast growth factor family
J Biol Chem
(1996)
Proliferation of intimal smooth muscle cells. Attenuation of basic fibroblast growth factor 2-stimulated proliferation is associated with increased expression of cell cycle inhibitors
J Biol Chem
Expressions of basic fibroblast growth factor and its receptors and their relationship to proliferation of human hepatocellular carcinoma cell lines
Hepatology
Correlation of serum basic fibroblast growth factor levels with clinicopathologic features and postoperative recurrence in hepatocellular carcinoma
Am J Surg
Small RNAcan RNA interference be exploited for therapy?
Lancet
Primary liver cancer. Asian experience
Hepatocellular carcinoma and hepatitis C in the United States
Hepatology
Prevention and treatment of hepatocellular carcinoma
Liver Transpl
Radiofrequency thermal ablation of hepatocellular carcinoma
Dig Dis
Nonsurgical treatment of hepatocellular carcinomafrom percutaneous ethanol injection therapy and percutaneous microwave coagulation therapy to radiofrequency ablation
Oncology
Role of surgery in the treatment of primary carcinoma of the livera 31-year experience
Br J Surg
Prognostic factors for survival in patients with compensated cirrhosis and small hepatocellular carcinoma after percutaneous ethanol injection therapy
Cancer
Interferon therapy after tumor ablation improves prognosis in patients with hepatocellular carcinoma associated with hepatitis C virus
Ann Intern Med
Prevention of second primary tumors by an acyclic retinoid, polyprenoic acid, in patients with hepatocellular carcinoma. Hepatoma Prevention Study Group
N Engl J Med
Growth inhibition of human hepatoma cells by acyclic retinoid is associated with induction of p21(CIP1) and inhibition of expression of cyclin D1
Cancer Res
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Supported in part by grants-in-aid for scientific research from the Japanese Ministry of Education, Culture, Sports, Science, and Technology and by Health and Labor Sciences Research Grants for Research on Hepatitis from the Ministry of Health, Labor, and Welfare of Japan.