1. Academic Validation
  2. Heterogeneous gene expression changes in colorectal cancer cells share the WNT pathway in response to growth suppression by APHS-mediated COX-2 inhibition

Heterogeneous gene expression changes in colorectal cancer cells share the WNT pathway in response to growth suppression by APHS-mediated COX-2 inhibition

  • Biologics. 2008 Jun;2(2):329-37. doi: 10.2147/btt.s2663.
Bostjan Humar 1 Les McNoe Anita Dunbier Rosemary Heathcott Antony W Braithwaite Anthony E Reeve
Affiliations

Affiliation

  • 1 Cancer Genetics Laboratory, Department of Biochemistry; University of Otago, Dunedin, Aotearoa New Zealand;
Abstract

Cyclooxygenase-2 (COX-2), the prostaglandin (PG)-synthesizing Enzyme overexpressed in colorectal Cancer (CRC), has pleiotropic, cancer-promoting effects. COX-2 inhibitors (CIBs) interfere with many cancer-associated processes and show promising antineoplastic activity, however, a common mechanism of CIB action has not yet been established. We therefore investigated by microarray the global response towards the CIB APHS at a dose significantly inhibiting the growth of three COX-2-positive CRC but not of two COX-2-negative cell lines. None of the genes significantly (p = 0.005) affected by APHS were common to all three cell lines and 83% of the altered pathways were cell line-specific. Quantitative polymerase chain reaction (QPCR) on selected pathways confirmed cell line-specific expression alterations induced by APHS. A low stringency data analysis approach using BRB array tools coupled with QPCR, however, identified small expression changes shared by all COX-2-positive cell lines in genes related to the Wnt pathway, the key driver of colonic carcinogenesis. Our data indicates a substantial cell line-specificity of APHS-induced expression alterations in CRC cells and helps to explain the divergent effects reported for CIBs. Further, the shared inhibition of the Wnt pathway by APHS suggests one potential common mechanism behind the antineoplastic effects of COX-2 inhibition.

Keywords

COX-2 inhibitors; DNA arrays; WNT factors; antineoplastic drugs; cell lines; colon cancer.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-129284
    COX-2 Inhibitor
    COX