SNU-484 위암 세포주를 이종이식한 Nude Mouse에 Docetaxel과 Capecitabine 복합항암 화학요법을 하는 경우 Docetaxel 투여방법의 변화에 따른 Thymidine Phosphorylase의 유도와 항암효과 상승기전에 관한 연구

Purpose: Docetaxel (Taxotere ⓡ ) and capecitabine are used in combination to treat advanced gastric cancer. Thymidine phosphorylase (TP) is an essential enzyme for the activation of capecitabine in tumors. This study sought to identify the best combination therapy with capecitabine and using two different schedules for docetaxel, a TP up-regulator, to enhance capecitabine’s efficacy. Methods: The human gastric cancer cell line SNU-484 was cultured and docetaxel (2㎍/㎖) was added to the 24-well plates that contained 5×105 cells/well. The total RNA was isolated and RT-PCR was done to identify the TP expression. Four- or five-week-old BALB/c-nu/nu mice were subcutaneously inoculated with the SNU-484 cells. The nude mice were divided into two groups and they were given capecitabine 539 ㎎/㎡ p.o. from days 1 to 14: Group 1 was given docetaxel 15 ㎎/㎡ i.v. on day 1; Group 2 was given docetaxel 7.5㎎/㎡ on days 1 and 8. Tumor tissues were excised on days 1, 8 and 15 to measure the TP and bcl-2 levels. Results: TP was expressed 2 hours after docetaxel administration. Group 2 had a higher TP concentration in the tumor tissues and a better antitumor effect than did Group 1. There was no difference in the bcl-2 concentration in the two groups. Conclusion: These results suggest that docetaxel stimulates the TP expression in tumor tissues and it enhances the antitumor activity of capecitabine. A weekly docetaxel injection with capecitabine administration can be used to treat gastric cancer more effectively than when docetaxel is injected once per cycle. Capecitabine had no bcl-2 suppressive effect in this study.