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Tumor Biology
Published in: Tumor Biology 8/2016

01-08-2016 | Original Article

A novel anti-alpha-fetoprotein single-chain variable fragment displays anti-tumor effects in HepG2 cells as a single agent or in combination with paclitaxel

Authors: Xiaonan Ji, Yanli Shen, Hao Sun, Xiangdong Gao

Published in: Tumor Biology | Issue 8/2016

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Abstract

Human hepatocellular carcinoma (HCC) has a high rate of tumor recurrence and metastasis, resulting in shortened survival time. The function of alpha-fetoprotein (AFP) as a regulatory factor in the growth of HCC cells has been well defined. The aim of this study was to investigate the use of a novel AFP-specific single-chain variable fragment that blocked AFP and inhibited HCC cell growth. The results indicated that the anti-AFP single-chain variable fragment (scFv) induced growth inhibition of AFP-expressing HCC cell lines in vitro through induction of G1 cell cycle arrest and apoptosis. The mechanism of apoptosis probably involved with blocking AFP internalization and regulation of the PTEN/PI3K/Akt signaling network. Moreover, the anti-AFP-scFv also effectively sensitized the HepG2 cells to paclitaxel (PTX) at a lower concentration. The combination effect of PTX and anti-AFP-scFv displayed a synergistic effect on HepG2 cells both in vitro and in vivo. Our results demonstrated that targeting AFP by specific antibodies has potential immunotherapeutic efficacy in human HCC.
Literature
1.
2.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed
3.
EASL-EORTC clinical practice guidelines. Management of hepatocellular carcinoma. J Hepatol. 2012;56:908–43.CrossRef
4.
5.
Gotoh M, Nakatani T, Masuda T, Mizuguchi Y, Sakamoto M, Tsuchiya R, et al. Prediction of invasive activities in hepatocellular carcinomas with special reference to alpha-fetoprotein and des-gamma-carboxyprothrombin. Jpn J Clin Oncol. 2003;33:522–6.CrossRefPubMed
6.
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
7.
Ma WJ, Wang HY, Teng LS. Correlation analysis of preoperative serum alpha-fetoprotein (AFP) level and prognosis of hepatocellular carcinoma (HCC) after hepatectomy. World J Surg Oncol. 2013;11:212.CrossRefPubMedPubMedCentral
8.
Hann HW, Fu X, Myers RE, Hann RS, Wan S, Kim SH, et al. Predictive value of alpha-fetoprotein in the long-term risk of developing hepatocellular carcinoma in patients with hepatitis b virus infection—results from a clinic-based longitudinal cohort. Eur J Cancer. 2012;48:2319–27.CrossRefPubMedPubMedCentral
9.
Zhu M, Guo J, Li W, Lu Y, Fu S, Xie X, et al. Hepatitis b virus × protein induces expression of alpha-fetoprotein and activates PI3K/MTOR signaling pathway in liver cells. Oncotarget. 2015;6:12196–208.CrossRefPubMedPubMedCentral
10.
Li P, Wang SS, Liu H, Li N, McNutt MA, Li G, et al. Elevated serum alpha fetoprotein levels promote pathological progression of hepatocellular carcinoma. World J Gastroenterol. 2011;17:4563–71.CrossRefPubMedPubMedCentral
11.
Mizejewski GJ. Review of the putative cell-surface receptors for alpha-fetoprotein: identification of a candidate receptor protein family. Tumour Biol. 2011;32:241–58.CrossRefPubMed
12.
Zhu M, Guo J, Li W, Xia H, Lu Y, Dong X, et al. HBX induced AFP receptor expressed to activate PI3K/Akt signal to promote expression of SRC in liver cells and hepatoma cells. BMC Cancer. 2015;15:362.CrossRefPubMedPubMedCentral
13.
Li M, Li H, Li C, Wang S, Jiang W, Liu Z, et al. Alpha-fetoprotein: a new member of intracellular signal molecules in regulation of the PI3K/Akt signaling in human hepatoma cell lines. Int J Cancer. 2011;128:524–32.CrossRefPubMed
14.
Zhu M, Guo J, Xia H, Li W, Lu Y, Dong X, et al. Alpha-fetoprotein activates Akt/MTOR signaling to promote CXCR4 expression and migration of hepatoma cells. Oncoscience. 2015;2:59–70.CrossRefPubMedPubMedCentral
15.
Wang S, Jiang W, Chen X, Zhang C, Li H, Hou W, et al. Alpha-fetoprotein acts as a novel signal molecule and mediates transcription of FN14 in human hepatocellular carcinoma. J Hepatol. 2012;57:322–9.CrossRefPubMed
16.
Urnov FD, Rebar EJ, Holmes MC, Zhang HS, Gregory PD. Genome editing with engineered zinc finger nucleases. Nat Rev Genet. 2010;11:636–46.CrossRefPubMed
17.
Mohr SE, Perrimon N. RNAi screening: new approaches, understandings, and organisms. Wiley Interdiscip Rev RNA. 2012;3:145–58.CrossRefPubMed
18.
Perez-Martinez D, Tanaka T, Rabbitts TH. Intracellular antibodies and cancer: new technologies offer therapeutic opportunities. Bioessays. 2010;32:589–98.CrossRefPubMed
19.
20.
Neri D, Petrul H, Winter G, Light Y, Marais R, Britton KE, et al. Radioactive labeling of recombinant antibody fragments by phosphorylation using human casein kinase ii and [gamma-32p]-ATP. Nat Biotechnol. 1996;14:485–90.CrossRefPubMed
21.
Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979;76:4350–4.CrossRefPubMedPubMedCentral
22.
Li H, Liu H, Wang Z, Liu X, Guo L, Huang L, et al. The role of transcription factors SP1 and YY1 in proximal promoter region in initiation of transcription of the mu opioid receptor gene in human lymphocytes. J Cell Biochem. 2008;104:237–50.CrossRefPubMed
23.
Jin ZJ. About the evaluation of drug combination. Acta Pharmacol Sin. 2004;25:146–7.PubMed
24.
Li M, Zhou S, Liu X, Li P, McNutt MA, Li G. Alpha-fetoprotein shields hepatocellular carcinoma cells from apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand. Cancer Lett. 2007;249:227–34.CrossRefPubMed
25.
26.
Mizejewski GJ. Nonsecreted cytoplasmic alpha-fetoprotein: a newly discovered role in intracellular signaling and regulation. An update and commentary. Tumour Biol. 2015;36:9857–64.CrossRefPubMed
27.
Tian A, Wilson GS, Lie S, Wu G, Hu Z, Hebbard L, et al. Synergistic effects of IAP inhibitor LCL161 and paclitaxel on hepatocellular carcinoma cells. Cancer Lett. 2014;351:232–41.CrossRefPubMed
28.
Jeong JY, Kim KS, Moon JS, Song JA, Choi SH, Kim KI, et al. Targeted inhibition of phosphatidyl inositol-3-kinase p110beta, but not p110alpha, enhances apoptosis and sensitivity to paclitaxel in chemoresistant ovarian cancers. Apoptosis. 2013;18:509–20.CrossRefPubMedPubMedCentral
Metadata
Title
A novel anti-alpha-fetoprotein single-chain variable fragment displays anti-tumor effects in HepG2 cells as a single agent or in combination with paclitaxel
Authors
Xiaonan Ji
Yanli Shen
Hao Sun
Xiangdong Gao
Publication date
01-08-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 8/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-4803-x

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