ＧＦＰ遺伝子導入ラット舌へん平上皮癌細胞株を用いた肺微小転移に対するＴＳ‐１の転移抑制効果

Abstract

[Purpose] Lung metastases in patients with tongue cancer are resistant to various therapies, resulting in poor outcomes. In the present study, we examined whether such lung metastases are controllable by adjuvant chemotherapy targeting micrometastases in the lung. We used a micrometastasis model using a rat tongue carcinoma cell line (RSC3) tagged with the green fluorescent protein gene (RSC3LM-GFP) in nude mice.[Methods] Lung metastases were formed after intravenous (i. v.) injection of 1 (3)×105 tumor cells in a low (high) metastasis model. TS-1 (5-fluorouracil derivative)(20mg/kg) was orally administered from day 1 Postinjection (early administration) and from day 7 post-injection (late administration) 5 times per week for 3 weeks. Mice bearing lung metastases underwent autopsy 4 weeks after injection, and the lungs were removed. The numbers of lung metastases were determined by GFP fluorescence.[Results] Lung metastasis including micrometastasis could be clearly visualized under illumination with blue light. In the low metastasis model, GFP-positive metastatic nodules in the lung were more strongly reduced by early TS-1 oral administration than by late administration (p<0.003). Survival was also much longer in mice with early TS-1 treatment than in those with late treatment in the low metastasis model (p<0.02), but not in the high metastasis model.[Conclusion] These results indicate that the sensitivity of lung metastases of tongue carcinoma to TS-1 depends on the timing of drug administration and the number of metastases. Small numbers of micrometastases in the lung at an early stage are most susceptible and can be effectively eliminated by chemotherapy targeting micrometastasis, leading to longer survival of mice.