YYB-101, a Humanized Antihepatocyte Growth Factor Monoclonal Antibody, Inhibits Ovarian Cancer Cell Motility and Proliferation

Anticancer Res. 2021 Feb;41(2):671-678. doi: 10.21873/anticanres.14818.

Abstract

Background/aim: Hepatocyte growth factor (HGF) acts as a key regulator in promoting ovarian cancer metastasis. Previously, we observed that YYB-101, a humanized anti-HGF antibody, effectively inhibits ovarian cancer cell migration, invasion, and progression. Here, we evaluated the signaling mechanisms affected by YYB-101 that are important in ovarian cancer cell progression.

Materials and methods: Using cell migration, invasion and proliferation assays, we evaluated the effects of YYB-101 on A2780/luc and SKOV3 cells. The effects of YYB-101 on signaling molecules were determined by immunocytochemistry and immunoblot analysis.

Results: YYB-101 inhibited HGF-induced ovarian cancer cell motility by down-regulating paxillin phosphorylation and actin-cytoskeleton rearrangement. Also, YYB-101 inhibited ovarian cancer cell proliferation by reducing c-MET phosphorylation and activating apoptosis in vitro and in vivo. These effects were significantly enhanced by combining YYB-101 treatment with paclitaxel, a standard chemotherapy drug.

Conclusion: YYB-101 can be examined as a new therapeutic agent for the treatment of patients with ovarian cancer.

Keywords: Hepatocyte growth factor; apoptosis; c-MET; humanized monoclonal antibody; ovarian cancer.

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents, Immunological / pharmacology*
  • Antineoplastic Agents, Immunological / therapeutic use
  • Apoptosis / drug effects
  • Carcinoma, Ovarian Epithelial / drug therapy*
  • Carcinoma, Ovarian Epithelial / metabolism
  • Carcinoma, Ovarian Epithelial / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Cytoskeleton / drug effects
  • Cytoskeleton / metabolism
  • Cytoskeleton / pathology
  • Female
  • Hepatocyte Growth Factor / antagonists & inhibitors*
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Proto-Oncogene Proteins c-met / metabolism
  • Signal Transduction
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • HGF protein, human
  • monoclonal antibody YYB-101
  • Hepatocyte Growth Factor
  • MET protein, human
  • Proto-Oncogene Proteins c-met