A novel form of anti-angiogenic molecular antibody drug induces apoptosis in myeloma cells after cultivation upon endothelial feeder cells

Leuk Res. 2021 Sep:108:106617. doi: 10.1016/j.leukres.2021.106617. Epub 2021 May 15.

Abstract

The present study aimed to investigate the ability of a novel form of the anti-angiogenic molecular antibody drug to induce Myeloma cell death after cultivation upon endothelial feeder cells. Bevacizumab-loaded chitosan (BCS) nanoparticles (NPs) were prepared by the ionic gelation method. Human U266 cell line and human umbilical vein endothelial cells were co-cultured for 72 h and treated with BCS nanoparticles (10μM) to study their impact on inhibition of cell growth and induction of apoptosis. Death assessments, P53 pro-apoptotic marker expression and the VEGF level were investigated by flow-cytometric analyses of the Annexin V, immunocytochemistry and ELISA, respectively. The endothelial monolayer co-culture showed protection of myeloma cells from apoptosis when exposed to NPs or without any treatment. In present of bevacizumab, the VEGF factor was effectively suppressed, and the p53 expression was significantly increased in bevacizumab-treated myeloma cells co-cultured with HUVECs, compared to other groups. BCS was capable of disturbing the effective interconnections of myeloma cells and HUVECs as supportive cells. Disruptions of tumor cells' connections with their microenvironment and blocking their possible supportive pathways might be a potential strategy to eradicate tumor cells and finally cure such types of cancer.

Keywords: Bevacizumab; Myeloma; Nanoparticles-loaded CS.

MeSH terms

  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / pharmacology
  • Apoptosis*
  • Bevacizumab / pharmacology*
  • Cell Proliferation
  • Coculture Techniques
  • Feeder Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Humans
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / pathology*
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / pathology

Substances

  • Angiogenesis Inhibitors
  • Bevacizumab