A neutralized human LMP1-IgG inhibits ENKTL growth by suppressing the JAK3/STAT3 signaling pathway

Oncotarget. 2017 Feb 14;8(7):10954-10965. doi: 10.18632/oncotarget.14032.

Abstract

Latent membrane protein 1 (LMP1), which is associated with the development of different types of Epstein-Barr virus (EBV) related lymphoma, has been suggested to be an important oncoprotein. In this study, a human anti-LMP1 IgG antibody (LMP1-IgG) was constructed and characterized by ELISA, western blotting (WB), affinity and immunohistochemistry (IHC) analyses. CCK-8, MTT, apoptosis assays, antibody-dependent cell-mediated cytotoxicity (ADCC) and CDC (complement-dependent cytotoxicity) assays were performed to evaluate the inhibitory effects of LMP1-IgG on extranodal nasal-type natural killer (NK)/T-cell lymphoma (ENKTL). Then, the influence of LMP1-IgG on the JAK/STAT signaling pathway was investigated. The results showed that the successfully constructed LMP1-IgG inhibited proliferation, induced apoptosis, and activated ADCC and CDC of ENKTL in a concentration- and time- dependent manner. Moreover, phosphorylation of JAK3 and STAT3 was inhibited by LMP1-IgG. Our data indicate that LMP1-IgG may provide a novel and promising therapeutic strategy for the treatment of LMP1-positive ENKTL.

Keywords: ENKTL; IgG; JAK/STAT; LMP1.

MeSH terms

  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / pharmacology
  • Antibody-Dependent Cell Cytotoxicity / drug effects
  • Apoptosis / drug effects
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunoglobulin G / immunology
  • Immunoglobulin G / pharmacology*
  • Immunohistochemistry
  • Janus Kinase 3 / metabolism*
  • Lymphoma, Extranodal NK-T-Cell / metabolism*
  • Lymphoma, Extranodal NK-T-Cell / pathology
  • Phosphorylation / drug effects
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects
  • Time Factors
  • Viral Matrix Proteins / immunology*

Substances

  • Antibodies, Neutralizing
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Immunoglobulin G
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Viral Matrix Proteins
  • JAK3 protein, human
  • Janus Kinase 3