Effects of oral UFT combined with or without zoledronic acid on bone metastasis in the 4T1/luc mouse breast cancer
| Autor: | Akimi Ueda, Kenji Hata, Toru Hiraga, Fumiyo Ikeda, Daisuke Tamura, Toshiyuki Yoneda, Paul J. Williams |
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| Rok vydání: | 2003 |
| Předmět: |
Antimetabolites
Antineoplastic Cancer Research Pathology medicine.medical_specialty medicine.medical_treatment Administration Oral Osteoclasts Antineoplastic Agents Apoptosis Bone Neoplasms Zoledronic Acid Tegafur Bone resorption Metastasis Mice Breast cancer medicine Animals Luciferases Uracil Mice Inbred BALB C Mice Inbred C3H Diphosphonates business.industry Imidazoles Mammary Neoplasms Experimental Bone metastasis Cancer Bisphosphonate medicine.disease Disease Models Animal Drug Combinations Zoledronic acid Oncology Cancer research Female Fluorouracil business medicine.drug |
| Zdroj: | International Journal of Cancer. 106:973-979 |
| ISSN: | 1097-0215 0020-7136 |
| DOI: | 10.1002/ijc.11330 |
| Popis: | Bone metastasis is one of the major causes of increased morbidity and eventual mortality in breast cancer patients. Therefore, intervention of bone metastases is one of the important targets in the management of breast cancer. In the present study, we examined the effects of the orally administrable chemotherapeutic agent UFT (a combination of tegafur and uracil at a molar ratio of 1:4) on bone metastases using an animal model of the 4T1/luc mouse breast cancer. The 4T1/luc cells developed spontaneous metastases to bone following orthotopic cell inoculation. Oral daily administration of UFT (20 mg/kg/day) significantly reduced the orthotopic tumor burden; however, the lower dose (15 mg/kg/day) did not. In contrast, histologic examination showed that both doses of UFT significantly suppressed bone metastases in a dose-dependent manner. Since clinical studies have demonstrated that bisphosphonates (BPs), specific inhibitors of osteoclastic bone resorption, are beneficial for breast cancer patients with bone metastases, we next examined the effects of UFT combined with the BP zoledronic acid (ZOL) on established bone metastases. The combination of UFT (20 mg/kg/day) with ZOL (250 microg/kg) caused an enhanced reduction of bone metastases compared with UFT alone. In vitro studies showed that 5-fluorouracil (5-FU), an active metabolite of UFT, and ZOL increased apoptosis in 4T1/luc cells and inhibited osteoclast-like cell formation in an additive fashion. Our results suggest that oral UFT is an effective chemotherapeutic agent for advanced breast cancer accompanying bone metastases and that the combination with BP increases its benefits for bone metastases. |
| Databáze: | OpenAIRE |
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