Abstract | BACKGROUND: MATERIALS AND METHODS: MCF-7 cells were treated with UCN-01, TAM, or UCN-01 combined with TAM at various concentrations in vitro. The antitumor effect was evaluated as the inhibition rate (I.R.%) by MTT assay. Two human breast carcinoma xenografts in nude mice, MCF-7 and Br-10, were treated with UCN-01, TAM or both agents together. The expression of p21 and the phosphorylation status of Rb protein in MCF-7 cells were detected by Western blotting. RESULTS:
UCN-01 or TAM alone inhibited the proliferation of MCF-7 cells in a concentration-dependent manner. Combined treatment with UCN-01 followed by TAM inhibited the growth of MCF-7 cells synergistically and no significant differences in cytotoxicity were observed between the different sequences of UCN-01/TAM and TAM/ UCN-01. Combination treatment with UCN-01 and TAM against MCF-7 and Br-10 in vivo exhibited superior antitumor effects compared with either agent treatment alone. Although 0.1 microg UCN-01 per ml (I.R.: 48.1%) or 2 microM TAM (I.R.: 31%) induced p21 expression, phosphorylation of Rb protein was not inhibited. However, combination treatment with UCN-01 and TAM at the same concentrations resulted in an I.R. of 67% and dephosphorylation of Rb protein. CONCLUSION: The present study suggests that combining UCN-01 and TAM could result in augmented cytotoxicity because of their similar mechanism of action. This combination may have potential clinical applications for breast cancer treatment, by reducing the toxicity of UCN-01.
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Authors | Junichi Koh, Tetsuro Kubota, Toshiko Koyama, Tomofusa Migita, Mitsumasa Hashimoto, Yoichiro Hosoda, Masaki Kitajima |
Journal | Breast cancer (Tokyo, Japan)
(Breast Cancer)
Vol. 10
Issue 3
Pg. 260-7
( 2003)
ISSN: 1340-6868 [Print] Japan |
PMID | 12955040
(Publication Type: Journal Article)
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Chemical References |
- Antineoplastic Agents
- Tamoxifen
- 7-hydroxystaurosporine
- Staurosporine
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Topics |
- Animals
- Antineoplastic Agents
(administration & dosage, pharmacology)
- Blotting, Western
- Breast Neoplasms
(drug therapy)
- Cell Line, Tumor
(drug effects)
- Dose-Response Relationship, Drug
- Drug Synergism
- Drug Therapy, Combination
- Female
- Humans
- Mice
- Mice, Inbred BALB C
- Staurosporine
(administration & dosage, analogs & derivatives, pharmacology)
- Tamoxifen
(administration & dosage, pharmacology)
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