Tumor Biology

, Volume 37, Issue 8, pp 10085–10096 | Cite as

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

Original Article

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.

Keywords

Hepatocellular carcinoma Alpha-fetoprotein Single-chain variable fragment Apoptosis Cell cycle arrest 

Notes

Acknowledgments

This work was supported by the Chinese Universities Scientific Fund (ZJ13083), the Fundamental Research Funds for the Central Universities (YD2014SK0002), and a project funded by the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions.

Compliance with ethical standards

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Xiaonan Ji
    • 1
  • Yanli Shen
    • 2
  • Hao Sun
    • 1
  • Xiangdong Gao
    • 1
  1. 1.School of Life Science and TechnologyChina Pharmaceutical UniversityNanjingChina
  2. 2.The People’s Hospital of PizhouXuzhouChina

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