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Cancer Chemotherapy and Pharmacology

Published in:

01-01-2010 | Original Article

Preclinical rationale for combined use of endocrine therapy and 5-fluorouracil but neither doxorubicin nor paclitaxel in the treatment of endocrine-responsive breast cancer

Authors: Junichi Kurebayashi, Mamoru Nukatsuka, Hiroshi Sonoo, Junji Uchida, Mamoru Kiniwa

Published in: Cancer Chemotherapy and Pharmacology | Issue 2/2010

Abstract

Purpose

Our previous study indicated that concurrent administration of 4-OH-tamoxifen (TAM) and 5-fluorouracil (5-FU), but not doxorubicin (Dox), resulted in additive antitumor effects on endocrine-responsive breast cancer cells. We further clarified the effects of combined administration of endocrine therapy with chemotherapeutic agents in this study.

Methods

Concurrent treatment with 4-OH-TAM and paclitaxel (Ptx) was investigated in estrogen receptor (ER)-positive breast cancer cells. Additionally, the combined effects of estrogen depletion from culture medium mimicking estrogen ablative therapy with 5-FU, Dox, and Ptx were investigated.

Results

Concurrent treatment with 4-OH-TAM and Ptx yielded less than additive antitumor effects in ER-positive breast cancer cells, as observed with Dox in our previous study. More interestingly, estrogen depletion with 5-FU, but with neither Dox nor Ptx, yielded additive antitumor effects on these cells. We also performed preliminary experiments to elucidate the mechanisms of action responsible for the combined antitumor effects observed. Ptx up-regulated the level of expression of one of the molecules related to TAM resistance, Eph-A2, as observed with Dox in our previous study. Estrogen depletion down-regulated the level of expression of one of the molecules related to 5-FU resistance, thymidylate synthase, as observed with 4-OH-TAM in our previous study.

Conclusions

These findings, together with those of our previous study, suggest that concurrent treatment with endocrine therapy, administration of TAM, or estrogen ablative therapy and 5-FU but neither Dox nor Ptx may yield additive antitumor effects on endocrine-responsive breast cancer.

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Title: Preclinical rationale for combined use of endocrine therapy and 5-fluorouracil but neither doxorubicin nor paclitaxel in the treatment of endocrine-responsive breast cancer
Authors: Junichi Kurebayashi
Mamoru Nukatsuka
Hiroshi Sonoo
Junji Uchida
Mamoru Kiniwa
Publication date: 01-01-2010
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 2/2010
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-009-1024-7

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