Synergistic Effect of Gefitinib and Temozolomide on U87MG Glioblastoma Angiogenesis

Nutr Cancer. 2022;74(4):1299-1307. doi: 10.1080/01635581.2021.1952441. Epub 2021 Jul 23.


One of the most common and deadly brain tumors is Glioblastoma multiforme (GBM). Due to recent advances in angiogenesis and its related key factors, this process as a hallmark in glioblastoma has attracted more consideration from the research community. Temozolomide (TMZ) as the first-line treatment used to treat GBM but, resistance to TMZ limits its effectiveness and the need for better treatments is still felt. Therefore, we aimed to examine the Synergistic effects of Gefitinib (GFI) in combination with Temozolomide on VEGF and MMPs in glioma cell line (U87MG). Our results displayed that GFI could induce cytotoxic effects in U87MG with IC50 values of 11 μM. U87MG cells produced large amounts of VEGF without any stimuli, and the results showed that GFI in combination with TMZ caused a significant decrease in VEGF production in these cells. In this study, we demonstrated that after treating with TMZ and GFI, there was more decrease in the levels of MMP 2 and 9 secretions in cells than treatment with GFI and TMZ doses alone. This study indicates synergistic effects of GFI plus TMZ against glioma are mediated by the potentiated anti-angiogenesis. Therefore, it can be considered as a promising plan for future studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Alkylating / pharmacology
  • Brain Neoplasms* / pathology
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm
  • Drug Synergism
  • Gefitinib / pharmacology
  • Gefitinib / therapeutic use
  • Glioblastoma* / pathology
  • Glioma* / drug therapy
  • Humans
  • Neovascularization, Pathologic / drug therapy
  • Temozolomide / pharmacology
  • Vascular Endothelial Growth Factor A / pharmacology


  • Antineoplastic Agents, Alkylating
  • Vascular Endothelial Growth Factor A
  • Gefitinib
  • Temozolomide