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.
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.
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Ji
authors.affiliation: The People's Hospital of Pizhou, Xuzhou, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Shen
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Sun
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, China. xdgao@cpu.edu.cn.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Gao
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004357:Drug Synergism; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008113:Liver Neoplasms / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D057127:Single-Chain Antibodies / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays; D000509:alpha-Fetoproteins / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D057127:Single-Chain Antibodies; D000509:alpha-Fetoproteins; D017239:Paclitaxel
keywords: Alpha-fetoprotein; Apoptosis; Cell cycle arrest; Hepatocellular carcinoma; Single-chain variable fragment
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