Preferential inhibition of bone metastases by 5'-deoxy-5-fluorouridine and capecitabine in the 4T1/luc mouse breast cancer model
| Autor: | Jirota Kitagaki, Toshiyuki Yoneda, Kenji Hata, Kaori Fujimoto-Ouchi, Yutaka Tanaka, Toru Hiraga, Fumiyo Ikeda |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Cancer Research
medicine.medical_specialty Time Factors Administration Oral Bone Neoplasms Transfection Deoxycytidine Capecitabine Mice Breast cancer Internal medicine Cell Line Tumor Antineoplastic Combined Chemotherapy Protocols medicine Animals Thymidine phosphorylase Luciferases Mice Inbred BALB C Oncogene Dose-Response Relationship Drug business.industry Bone metastasis Cancer Mammary Neoplasms Experimental General Medicine medicine.disease Endocrinology Treatment Outcome Oncology Uridine phosphorylase Systemic administration Cancer research Female Fluorouracil business Floxuridine medicine.drug |
| Zdroj: | Oncology reports. 14(3) |
| ISSN: | 1021-335X |
| Popis: | 5'-deoxy-5-fluorouridine (5'-DFUR) and capecitabine are oral anti-cancer agents, which are enzymatically converted to 5-fluorouracil (5-FU) by thymidine phosphorylase in humans and uridine phosphorylase in mice. Since the activity of these phosphorylases is higher in cancerous tissue than in normal tissue, systemic administration of 5'-DFUR and capecitabine achieves high intratumoral 5-FU levels and low adverse effects on non-tumoral tissue. Accordingly, 5'-DFUR and capecitabine are widely used for the treatment of cancer patients. In the present study, we examined the effects of 5'-DFUR and capecitabine on bone metastases, one of the most common complications of breast cancer, using an animal model in which inoculation of 4T1/luc mouse breast cancer cells into the mammary fat pads of female BALB/c mice developed spontaneous metastases in distant organs including bone, lung and liver. Mice received 4T1/luc cell inoculation in the mammary fat pad at day 0 and oral 5'-DFUR (31, 62, 123 or 246 mg/kg) or capecitabine (90, 180 or 359 mg/kg) daily from day 7 to day 21. Both 5'-DFUR and capecitabine significantly inhibited orthotopic tumor formation and distant metastases to bone, lung and liver in a dose-dependent manner. Of note, the lowest dose of 5'-DFUR (31 mg/kg) and capecitabine (90 mg/kg), which failed to inhibit orthotopic tumor development and the lung and liver metastases, significantly reduced the bone metastases. In conclusion, our results suggest that oral 5'-DFUR and capecitabine are effective for the treatment of primary and secondary breast tumors. Most notably, they also suggest that these agents are preferentially beneficial for bone metastases. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|