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Eur J Cancer. 2006 Dec;42(18):3267-73. Epub 2006 Sep 6.

Tissue inhibitor of metalloproteinase-3 induces apoptosis in prostate cancer cells and confers increased sensitivity to paclitaxel.

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Department of Urology, Wayne State University School of Medicine, Detroit, MI 48201, USA.


Prostate cancer is the most common cancer and the second leading cause of cancer-related death in American men. To investigate the possible usefulness of tissue inhibitor of metalloproteinase-3 (TIMP-3) in prostate cancer gene therapy, we used an adenovirus expressing TIMP-3 to assess its role as an apoptosis trigger in highly metastatic prostate cancer cell lines PC-3 and DU-145. We showed that TIMP-3 alone induced apoptotic cell death which was triggered by mitochondrion-mediated caspase-3 activation. In combination treatment, we found that adenovirus-mediated expression of TIMP-3 greatly sensitised prostate cancer cells to chemotherapeutic drug paclitaxel, indicating a superadditive or synergistic effect of TIMP-3 and cytostatic treatment on prostate cancer cell death. The proper combination of adenovirus-mediated expression of TIMP-3 with conventional chemotherapeutic drug(s) could have potential benefits in treating highly metastatic prostate cancer.

[Indexed for MEDLINE]

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