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UFT inhibits lung metastases in spontaneous metastasis model of lung cancer
R Miyahara1, T Nakagawa, S Ishikawa
1Department of Thoracic Surgery, Kyoto University, Sakyo-ku, Kyoto, Japan.
Background:
UFT, an oral 5-fluorouracil derivative, is the only drug that is effective as a postoperative adjuvant therapy for non-small cell lung cancer (NSCLC) [ ], but the mechanism of the action remains unclear. We examined whether UFT and/or its metabolite, gamma-hydroxybutyric acid (GHB) inhibits lung metastases in a mouse model.
Methods:
Lewis lung carcinoma cells were implanted into the foot pads of C57 BL/6 mice, and mice were treated with UFT or GHB.
Results:
Both the mean number of metastatic nodules and the mean lung weight for UFT-treated mice (11.4 and 192.1 mg, respectively) were significantly lower than those for saline-treated mice (41.5 and 415.0 mg, respectively) (p < 0.001 for both). UFT did not inhibit tumor growth at the primary sites (foot pads). No significant body weight loss was documented in UFT-treated mice. GHB did not inhibit development of lung metastases even when a higher dose was used.
Conclusions:
UFT inhibits development of lung metastases without any toxicity in mouse model, which may explain the efficacy of postoperative administration of UFT for resected NSCLC.
Insights
UFT effectively reduces lung metastases in a mouse model of non-small cell lung cancer (NSCLC) without causing toxicity. This study suggests UFT
Area of Science:
- Oncology
- Pharmacology
- Cancer Metastasis Research
Background:
- UFT (uracil and tegafur) is a key postoperative adjuvant therapy for non-small cell lung cancer (NSCLC).
- The precise mechanism of UFT's action in preventing cancer spread is not fully understood.
- Investigating UFT and its metabolite gamma-hydroxybutyric acid (GHB) effects on lung metastasis is crucial.
Purpose of the Study:
- To determine if UFT or its metabolite GHB can inhibit lung metastasis in a preclinical mouse model.
- To elucidate the mechanism behind UFT's efficacy in treating resected NSCLC.
Main Methods:
- Lewis lung carcinoma cells were implanted into C57 BL/6 mice.
- Mice received treatment with either UFT or GHB, alongside a control group receiving saline.
- Tumor growth, lung metastasis, and body weight were monitored.
Main Results:
- UFT significantly reduced the number of lung metastatic nodules and mean lung weight compared to controls (p < 0.001).
- UFT did not inhibit primary tumor growth in the foot pads.
- No significant body weight loss was observed in UFT-treated mice.
- GHB showed no inhibitory effect on lung metastasis development.
Conclusions:
- UFT demonstrates efficacy in inhibiting lung metastasis development in a mouse model.
- The anti-metastatic effect of UFT occurs without observable toxicity.
- These findings support the use of UFT as a postoperative adjuvant therapy for resected NSCLC.
