Inhibition of the Akt, cyclooxygenase-2, and matrix metalloproteinase-9 pathways in combination with androgen deprivation therapy: Potential therapeutic approaches for prostate cancer

Hiroshi Miyamoto, Saleh Altuwaijri, Yi Cai, Edward M. Messing, Chawnshang Chang

Research output: Contribution to journalReview articlepeer-review

Abstract

Prostate cancer cells are generally dependent on androgen stimulation mediated by the androgen receptor (AR) for growth and survival, and, therefore, hormonal manipulation, such as castration and/or the use of AR antagonists, results in a regression of the cancer. However, this treatment very rarely leads to the "cure" of advanced disease, and cancers eventually become androgen-independent. A number of genes/pathways have been reported to be activated in prostate cancer, most of which are possibly associated with disease progression. In this article, among them, we focus on Akt (also known as protein kinase B), cyclooxygenase (COX)-2, and matrix metalloproteinase (MMP)-9, whose activities or expressions have been found to be regulated by androgens/AR. Previous studies by us and others, with androgen-sensitive prostate cancer cell lines, have demonstrated that androgen deprivation results in activation/ overexpression of Akt, COX-2, and MMP-9 in cells. This suggests that androgen deprivation in clinical settings activates the Akt, COX-2, and MMP-9 pathways in prostate cancer, which may increase cell growth and in turn promote the transition to the androgen-independent state. We hypothesize that androgen deprivation, in combination with inhibition of the Akt, COX-2, and MMP-9 pathways, delays the androgen-independent transition and has more beneficial effects than hormonal therapy alone.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalMolecular Carcinogenesis
Volume44
Issue number1
DOIs
StatePublished - Sep 1 2005

Keywords

  • Akt
  • Androgen deprivation therapy
  • COX-2
  • MMP-9
  • Prostate cancer

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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