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 Nguyen

Research output: Contribution to journalArticle

24 Citations (Scopus)

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

Fingerprint

2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Mitogen-Activated Protein Kinase Kinases
Phosphatidylinositol 3-Kinases
Vascular Endothelial Growth Factor A
Neoplasm Metastasis
Cell Movement
Phenotype
Cell Proliferation
Annexin A5
Conditioned Culture Medium
Epidermal Growth Factor
Wound Healing
Phosphotransferases
Enzyme-Linked Immunosorbent Assay
U 0126
Malignant Mesothelioma
Therapeutics
Pharmaceutical Preparations
Neoplasms
matrigel

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Suppression of pro-metastasis phenotypes expression in malignant pleural mesothelioma by the PI3K inhibitor LY294002 or the MEK inhibitor UO126. / Cole, George W.; Alleva, Annette M.; Zuo, Jing T.; Sehgal, Shailen S.; Yeow, Wen Shuz; Schrump, David S.; Nguyen, Dao.

In: Anticancer Research, Vol. 26, No. 2 A, 01.03.2006, p. 809-821.

Research output: Contribution to journalArticle

Cole, George W. ; Alleva, Annette M. ; Zuo, Jing T. ; Sehgal, Shailen S. ; Yeow, Wen Shuz ; Schrump, David S. ; Nguyen, Dao. / Suppression of pro-metastasis phenotypes expression in malignant pleural mesothelioma by the PI3K inhibitor LY294002 or the MEK inhibitor UO126. In: Anticancer Research. 2006 ; Vol. 26, No. 2 A. pp. 809-821.
@article{c0f394e42e034a419974fa35d46c6a7a,
title = "Suppression of pro-metastasis phenotypes expression in malignant pleural mesothelioma by the PI3K inhibitor LY294002 or the MEK inhibitor UO126",
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.",
keywords = "Angiogenesis, Apoptosis, EGFR, ERK1/2, MAPK, MEK, MEK inhibitor UO126, Motility, PI3K inhibitor LY294002, Prometastasis phenotypes",
author = "Cole, {George W.} and Alleva, {Annette M.} and Zuo, {Jing T.} and Sehgal, {Shailen S.} and Yeow, {Wen Shuz} and Schrump, {David S.} and Dao Nguyen",
year = "2006",
month = "3",
day = "1",
language = "English",
volume = "26",
pages = "809--821",
journal = "Anticancer Research",
issn = "0250-7005",
publisher = "International Institute of Anticancer Research",
number = "2 A",

}

TY - JOUR

T1 - Suppression of pro-metastasis phenotypes expression in malignant pleural mesothelioma by the PI3K inhibitor LY294002 or the MEK inhibitor UO126

AU - Cole, George W.

AU - Alleva, Annette M.

AU - Zuo, Jing T.

AU - Sehgal, Shailen S.

AU - Yeow, Wen Shuz

AU - Schrump, David S.

AU - Nguyen, Dao

PY - 2006/3/1

Y1 - 2006/3/1

N2 - 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.

AB - 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.

KW - Angiogenesis

KW - Apoptosis

KW - EGFR

KW - ERK1/2

KW - MAPK

KW - MEK

KW - MEK inhibitor UO126

KW - Motility

KW - PI3K inhibitor LY294002

KW - Prometastasis phenotypes

UR - http://www.scopus.com/inward/record.url?scp=33645805911&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645805911&partnerID=8YFLogxK

M3 - Article

C2 - 16619474

AN - SCOPUS:33645805911

VL - 26

SP - 809

EP - 821

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

IS - 2 A

ER -