Effects of sequential treatments with chemotherapeutic drugs followed by TRAIL on prostate cancer in vitro and in vivo.
Abstract | BACKGROUND: METHODS: Prostate and bladder cancer cells were exposed to chemotherapeutic drugs ( paclitaxel, vincristine, vinblastine, etoposide, doxorubicin, and camptothecin) and TRAIL. Cell viability was measured by sodium 3'[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis (4-methoxy-6-nitro) assay; expressions of death receptors and Bcl-2 family members were measured by Western blotting, ELISA and ribonuclease protection assay. PC-3 tumor cells xenografted athymic nude mice were exposed to chemotherapeutic drugs and TRAIL, either alone or in combination, to measure tumor growth and survival of mice. Apoptosis was measured by annexin V-FITC/ propidium iodide staining, and terminal deoxynucleotidyltransferase-mediated nick end labeling assay. Caspase-3 activity was measured by the Western blotting and immunohistochemistry. RESULTS: TRAIL induced apoptosis with varying sensitivity. Chemotherapeutic drugs ( paclitaxel, vincristine, vinblastine, etoposide, doxorubicin, and camptothecin) significantly augmented TRAIL-induced apoptosis in cancer cells through up-regulation of DR4, DR5, Bax, and Bak, and induction of caspase activation. Mitochondrial pathway enhanced the synergistic interactions between drugs and TRAIL. The sequential treatment of mice with chemotherapeutic drugs followed by TRAIL induced caspase-3 activity, and apoptosis, inhibited angiogenesis, completely eradicated the established tumors, and enhanced survival of mice. CONCLUSIONS: Chemotherapeutic drugs can be used to enhance the therapeutic potential of TRAIL in prostate cancer.
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Authors | Sharmila Shankar, Xufen Chen, Rakesh K Srivastava |
Journal | The Prostate
(Prostate)
Vol. 62
Issue 2
Pg. 165-86
(Feb 01 2005)
ISSN: 0270-4137 [Print] United States |
PMID | 15389801
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Copyright | Copyright 2004 Wiley-Liss, Inc. |
Chemical References |
- Androgens
- Antineoplastic Agents
- Apoptosis Regulatory Proteins
- Membrane Glycoproteins
- Proto-Oncogene Proteins c-bcl-2
- Receptors, TNF-Related Apoptosis-Inducing Ligand
- Receptors, Tumor Necrosis Factor
- TNF-Related Apoptosis-Inducing Ligand
- TNFRSF10A protein, human
- TNFRSF10B protein, human
- TNFSF10 protein, human
- Tnfrsf10b protein, mouse
- Tnfsf10 protein, mouse
- Tumor Necrosis Factor-alpha
- CASP3 protein, human
- Casp3 protein, mouse
- Caspase 3
- Caspases
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Topics |
- Androgens
(metabolism)
- Animals
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects)
- Apoptosis Regulatory Proteins
- Caspase 3
- Caspases
(metabolism)
- Drug Synergism
- Humans
- In Vitro Techniques
- Male
- Membrane Glycoproteins
(pharmacology)
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Mitochondria
(drug effects, physiology)
- Neovascularization, Pathologic
(drug therapy, mortality)
- Prostatic Neoplasms
(drug therapy, mortality)
- Proto-Oncogene Proteins c-bcl-2
(metabolism)
- Receptors, TNF-Related Apoptosis-Inducing Ligand
- Receptors, Tumor Necrosis Factor
(metabolism)
- Survival Rate
- TNF-Related Apoptosis-Inducing Ligand
- Tumor Necrosis Factor-alpha
(pharmacology)
- Urinary Bladder Neoplasms
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