Skip to main content
Top
Published in: Tumor Biology 5/2014

01-05-2014 | Research Article

Effects of AFP-activated PI3K/Akt signaling pathway on cell proliferation of liver cancer

Authors: Lu Zheng, Wei Gong, Ping Liang, XiaoBing Huang, Nan You, Ke Qiang Han, Yu Ming Li, Jing Li

Published in: Tumor Biology | Issue 5/2014

Login to get access

Abstract

This study aims to investigate effects of alpha-fetoprotein (AFP)-activated phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway on hepatocellular carcinoma cell proliferation. Active cirrhosis patients after hepatitis B infection (n = 20) and viral hepatitis patients with hepatocellular carcinoma (HCC) (n = 20) were selected as the subjects of the present study. Another 20 healthy subjects were selected as the control group. The serum AFP expression and liver tissue PI3K and Akt gene mRNA expression were detected. The hepatoma cell model HepG2 which had a stable expression of AFP gene was used. Real-time quantitative PCR and Western blot and other methods were used to analyze the intracellular PI3K and Akt protein levels. Compared with control group and cirrhosis group, the serum AFP levels in HCC group significantly increased, and the tissue PI3K and Akt mRNA expression also significantly increased. HepG2 cells were intervened using AFP, in which the PIK and Akt protein expression significantly increased. After intervention by use of AFP monoclonal antibodies or LY294002 inhibitor, the PIK and Akt protein expression in HepG2 cell was significantly decreased (P < 0.05). AFP can promote the proliferation of hepatoma cells via activation of PI3K/Akt signaling pathway.
Literature
1.
go back to reference Zhao Y, Wang Q, Deng X, Shi P, Wang Z. Quantitative assessment of the association between GSTP1 gene Ile105Val polymorphism and susceptibility to hepatocellular carcinoma. Tumour Biol. 2013;34:2121–6.CrossRefPubMed Zhao Y, Wang Q, Deng X, Shi P, Wang Z. Quantitative assessment of the association between GSTP1 gene Ile105Val polymorphism and susceptibility to hepatocellular carcinoma. Tumour Biol. 2013;34:2121–6.CrossRefPubMed
2.
go back to reference Wu D, Jiang H, Gu Q, Zhang D, Li Z. Association between XRCC1 Arg399Gln polymorphism and hepatitis virus-related hepatocellular carcinoma risk in Asian population. Tumour Biol. 2013;34:3265–9.CrossRefPubMed Wu D, Jiang H, Gu Q, Zhang D, Li Z. Association between XRCC1 Arg399Gln polymorphism and hepatitis virus-related hepatocellular carcinoma risk in Asian population. Tumour Biol. 2013;34:3265–9.CrossRefPubMed
3.
go back to reference Xia GL, Liu CB, Cao HL, et al. Prevalence of hepatitis B and C virus infections in the general Chinese population. Int Hepatol Commun. 1996;5:62–73.CrossRef Xia GL, Liu CB, Cao HL, et al. Prevalence of hepatitis B and C virus infections in the general Chinese population. Int Hepatol Commun. 1996;5:62–73.CrossRef
4.
go back to reference Montalto G, Iovanna JL, Soresi M, Dusetti N, Carroccio A, Barthelemy-Bialas S, et al. Clinical evaluation of pancreatitis-associated protein as a serum marker of hepatocellular carcinoma: comparison with alpha-fetoprotein. Oncology. 1998;55:421–5.CrossRefPubMed Montalto G, Iovanna JL, Soresi M, Dusetti N, Carroccio A, Barthelemy-Bialas S, et al. Clinical evaluation of pancreatitis-associated protein as a serum marker of hepatocellular carcinoma: comparison with alpha-fetoprotein. Oncology. 1998;55:421–5.CrossRefPubMed
5.
go back to reference McMahon BJ. Epidemiology and natural history of hepatitis B. Semin Liver Dis. 2005;25(suppl):3–8.CrossRefPubMed McMahon BJ. Epidemiology and natural history of hepatitis B. Semin Liver Dis. 2005;25(suppl):3–8.CrossRefPubMed
6.
go back to reference Schmelzer E, Zhang L, Bruce A, et al. Human hepatic stem cells from fetal and postnatal donors. Hepatology. 2007;46:2042–4.CrossRef Schmelzer E, Zhang L, Bruce A, et al. Human hepatic stem cells from fetal and postnatal donors. Hepatology. 2007;46:2042–4.CrossRef
7.
go back to reference Mizejewski GJ. Alpha-fetoprotein structure and function: relevance to isoforms, epitopes, and conformational variants. Exp Biol Med (Maywood). 2001;226:377–408. Mizejewski GJ. Alpha-fetoprotein structure and function: relevance to isoforms, epitopes, and conformational variants. Exp Biol Med (Maywood). 2001;226:377–408.
8.
go back to reference Si S, Sun Y, Li Z, et al. Gene therapy by membrane-expressed superantigen for alpha-fetoprotein-producing hepatocellular carcinoma. Gene Ther. 2006;13:1603–10.CrossRefPubMed Si S, Sun Y, Li Z, et al. Gene therapy by membrane-expressed superantigen for alpha-fetoprotein-producing hepatocellular carcinoma. Gene Ther. 2006;13:1603–10.CrossRefPubMed
9.
go back to reference Li MS, Li PF, Chen Q, Du GG, Li G. Alpha-fetoprotein stimulated the expression of some oncogenes in human hepatocellular carcinoma Bel 7402 cells. World J Gastroenterol. 2004;10:819–24.PubMedPubMedCentral Li MS, Li PF, Chen Q, Du GG, Li G. Alpha-fetoprotein stimulated the expression of some oncogenes in human hepatocellular carcinoma Bel 7402 cells. World J Gastroenterol. 2004;10:819–24.PubMedPubMedCentral
10.
go back to reference Zhang XL, Shi JQ, Zuo SH. A comparative study of the expression of ras oncogenic protein P21 and oncofetal protein AFP, CEA in human hepatocellular carcinoma (HCC). Zhonghua Bing Li Xue Za Zhi. 1994;23:155–8.PubMed Zhang XL, Shi JQ, Zuo SH. A comparative study of the expression of ras oncogenic protein P21 and oncofetal protein AFP, CEA in human hepatocellular carcinoma (HCC). Zhonghua Bing Li Xue Za Zhi. 1994;23:155–8.PubMed
11.
go back to reference Semenkova LN, Dudich EI, Dudich IV, et al. Alpha-fetoprotein as a TNF-resistance factor for human hepato-carcinoma cell line HepG2. Tumor Biol. 1997;18:30–40.CrossRef Semenkova LN, Dudich EI, Dudich IV, et al. Alpha-fetoprotein as a TNF-resistance factor for human hepato-carcinoma cell line HepG2. Tumor Biol. 1997;18:30–40.CrossRef
12.
go back to reference Abdel-Hamid NM, Mohafez OM, Zakaria S, Thabet K. Hepatic somatostatin receptor 2 expression during premalignant stages of hepatocellular carcinoma. Tumour Biol. 2013. doi:10.1007/s13277-013-1330-x Abdel-Hamid NM, Mohafez OM, Zakaria S, Thabet K. Hepatic somatostatin receptor 2 expression during premalignant stages of hepatocellular carcinoma. Tumour Biol. 2013. doi:10.​1007/​s13277-013-1330-x
13.
go back to reference Li F, Fan YC, Gao S, Sun FK, Yang Y, Wang K. Methylation of serum insulin-like growth factor-binding protein 7 promoter in hepatitis B virus-associated hepatocellular carcinoma. Genes Chromosom Cancer. 2014;53:90–7.CrossRefPubMed Li F, Fan YC, Gao S, Sun FK, Yang Y, Wang K. Methylation of serum insulin-like growth factor-binding protein 7 promoter in hepatitis B virus-associated hepatocellular carcinoma. Genes Chromosom Cancer. 2014;53:90–7.CrossRefPubMed
14.
go back to reference Yau WY, Shih HC, Tsai MH, Sheu JC, Chen CH, Chow LP. Autoantibody recognition of an N-terminal epitope of hnRNP L marks the risk for developing HBV-related hepatocellular carcinoma. J Proteomics. 2013;94C:346–58.CrossRef Yau WY, Shih HC, Tsai MH, Sheu JC, Chen CH, Chow LP. Autoantibody recognition of an N-terminal epitope of hnRNP L marks the risk for developing HBV-related hepatocellular carcinoma. J Proteomics. 2013;94C:346–58.CrossRef
15.
go back to reference Giovannini C, Baglioni M, Baron Toaldo M, Ventrucci C, D'Adamo S, Cipone M, et al. Notch3 inhibition enhances sorafenib cytotoxic efficacy by promoting GSK3b phosphorylation and p21 down-regulation in hepatocellular carcinoma. Oncotarget. 2013;4:1618–31.CrossRefPubMedPubMedCentral Giovannini C, Baglioni M, Baron Toaldo M, Ventrucci C, D'Adamo S, Cipone M, et al. Notch3 inhibition enhances sorafenib cytotoxic efficacy by promoting GSK3b phosphorylation and p21 down-regulation in hepatocellular carcinoma. Oncotarget. 2013;4:1618–31.CrossRefPubMedPubMedCentral
16.
go back to reference Fu Z, Ren L, Wei H, Lv J, Che X, Zhu Z, Jia J, Wang L, Lin G, Lu R, Yao Z. Effects of Tyroserleutide on phosphatidylinositol 3′-kinase/AKT pathway in human hepatocellular carcinoma cell. J Drug Target. 2014;22:146–55. Fu Z, Ren L, Wei H, Lv J, Che X, Zhu Z, Jia J, Wang L, Lin G, Lu R, Yao Z. Effects of Tyroserleutide on phosphatidylinositol 3′-kinase/AKT pathway in human hepatocellular carcinoma cell. J Drug Target. 2014;22:146–55.
17.
go back to reference Colombino M, Sperlongano P, Izzo F, Tatangelo F, Botti G, Lombardi A, et al. BRAF and PIK3CA genes are somatically mutated in hepatocellular carcinoma among patients from South Italy. Cell Death Dis. 2012;3:e259.CrossRefPubMedPubMedCentral Colombino M, Sperlongano P, Izzo F, Tatangelo F, Botti G, Lombardi A, et al. BRAF and PIK3CA genes are somatically mutated in hepatocellular carcinoma among patients from South Italy. Cell Death Dis. 2012;3:e259.CrossRefPubMedPubMedCentral
18.
go back to reference Wang RY, Chen L, Chen HY, Hu L, Li L, Sun HY, et al. MUC15 inhibits dimerization of EGFR and PI3K-AKT signaling and is associated with aggressive hepatocellular carcinomas in patients. Gastroenterology. 2013;145:1436–48.CrossRefPubMed Wang RY, Chen L, Chen HY, Hu L, Li L, Sun HY, et al. MUC15 inhibits dimerization of EGFR and PI3K-AKT signaling and is associated with aggressive hepatocellular carcinomas in patients. Gastroenterology. 2013;145:1436–48.CrossRefPubMed
19.
go back to reference Wang XJ, Feng CW, Li M. ADAM17 mediates hypoxia-induced drug resistance in hepatocellular carcinoma cells through activation of EGFR/PI3K/Akt pathway. Mol Cell Biochem. 2013;380:57–66.CrossRefPubMed Wang XJ, Feng CW, Li M. ADAM17 mediates hypoxia-induced drug resistance in hepatocellular carcinoma cells through activation of EGFR/PI3K/Akt pathway. Mol Cell Biochem. 2013;380:57–66.CrossRefPubMed
Metadata
Title
Effects of AFP-activated PI3K/Akt signaling pathway on cell proliferation of liver cancer
Authors
Lu Zheng
Wei Gong
Ping Liang
XiaoBing Huang
Nan You
Ke Qiang Han
Yu Ming Li
Jing Li
Publication date
01-05-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 5/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1535-z

Other articles of this Issue 5/2014

Tumor Biology 5/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine