Suppression of pro-metastasis phenotypes expression in malignant pleural mesothelioma by the PI3K inhibitor LY294002 or the MEK inhibitor UO126

George W. Cole, Annette M. Alleva, Jing T. Zuo, Shailen S. Sehgal, Wen Shuz Yeow, David S. Schrump, Dao M. Nguyen

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Background: This study aimed to evaluate the impact of selective abrogation of either the MEK/ERK1/2 (UO126 or PD98059) or the PI3/AKT (LY294002) signaling cascade on cell proliferation, motility and invasion and production of VEGF (collectively termed pro-metastasis phenotypes) in cultured malignant pleural mesothelioma (MPM) cells. Materials and Methods: Treatment-induced cytotoxicity was evaluated by MTT or Annexin V assays. Cell motility was assessed by wound healing and Matrigel invasion assays. VEGF in conditioned media of cancer cells was measured by ELISA. Results: LY294002 and UO126 significantly inhibited cell proliferation and clonogenicity of MPM cells in vitro. A substantial reduction of cell motility, Matrigel invasion as well as inhibition of basal or EGF-induced VEGF production were observed in drug-treated cells. Conclusion: The selective MEK or PI3K kinase inhibitors are equally effective in down-regulating the expression of pro-metastasis phenotypes, suggesting that MEK or PI3K are appropriate targets for the development of molecular therapeutics for malignant pleural mesothelioma.

Original languageEnglish (US)
Pages (from-to)809-821
Number of pages13
JournalAnticancer research
Volume26
Issue number2 A
StatePublished - Mar 1 2006
Externally publishedYes

Keywords

  • Angiogenesis
  • Apoptosis
  • EGFR
  • ERK1/2
  • MAPK
  • MEK
  • MEK inhibitor UO126
  • Motility
  • PI3K inhibitor LY294002
  • Prometastasis phenotypes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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