TRAIL: A Novel Therapeutic Agent for Prostate Cancer
Abstract
This study aims to elucidate the signaling pathway of TRAIL-mediated apoptosis in prostate cancer cells, and to examine the therapeutic effect of TRAIL on prostate cancer cells in vitro and in vivo. We found that most of prostate cancer cells such as androgen-independent PC-3 and DU145 cells are sensitive to TRAIL treatment while normal prostate epithelial cells are resistant. This result indicates that TRAIL may be appropriate agent for treatment of late-stage prostate cancer with no cytotoxicity to normal prostate cells. Further investigation on the molecular mechanism of TRAIL resistance revealed that pro-survival protein kinase Akt existed in a constitutively active form at high level in LNCaP cells that are resistant to TRAIL. Inhibition of PI 3-kinase sensitized LNCaP cells to TRAIL, suggesting that Akt may play a critical regulatory role in TRAIL signaling. To further understand the working mechanism of Akt, we surveyed its downstream targets, and found that the elevated eNOS activity by Akt phosphorylation may partially contribute to Akt-mediated TRAIL resistance in LNCaP cells. Our preliminary result also indicated that other anti-apoptotic mechanisms may exist in LNCaP cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2002
- Accession Number
- ADA406826
Entities
People
- Honglin Li
Organizations
- Ann & Robert H. Lurie Children's Hospital of Chicago