Tissue inhibitor of metalloproteinase-3 induces apoptosis in prostate cancer cells and confers increased sensitivity to paclitaxel.
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.
Deng
Xiyun
X
Department of Urology, Wayne State University School of Medicine, Detroit, MI 48201, USA. deng_xiyun@yahoo.com
Bhagat
Sunita
S
Dong
Zhong
Z
Mullins
Chadwick
C
Chinni
Sreenivasa Rao
SR
Cher
Michael
M
D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D004357:Drug Synergism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D017239:Paclitaxel / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D009363:Neoplasm Proteins; D019717:Tissue Inhibitor of Metalloproteinase-3; D020169:Caspases; D017239:Paclitaxel