Anticancer Research. 2006 Mar-Apr;26(2A):809-21. [Link]
Cole GW Jr, Alleva AM, Zuo JT, Sehgal SS, Yeow WS, Schrump DS, Nguyen DM.
Section of Thoracic Oncology, Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Background: This study aimed to evaluate the impact of selective abrogation of either the MEK/ERK1/2 (UO126 or PD98059) or the PI3K/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.