J Korean Surg Soc.  2007 Oct;73(4):294-301.

The Schedule Dependency for Induction of Thymidine Phosphorylase Activity and the Enhancement of Capecitabine Efficacy by Docetaxel on the SNU-484 Gastric Cancer Cell Line That was Injected into Xenografted Nude Mice

• Suh SB
• Suh BJ
• Kim JH
• Yoo HJ

Abstract

PURPOSE: Docetaxel (Taxotere(R)) 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 microgram/ml) was added to the 24-well plates that contained 5 x 10(5) 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 mg/m2 p.o. from days 1 to 14: Group 1 was given docetaxel 15 mg/m2 i.v. on day 1; Group 2 was given docetaxel 7.5mg/m2 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.

Keyword

Stomach cancer; Capecitabine; Docetaxel; Thymidine phosphorylase (TP); bcl-2

MeSH Terms

Animals
Appointments and Schedules*
Capecitabine
Cell Line*
Heterografts*
Humans
Mice
Mice, Nude*
RNA
Stomach Neoplasms*
Thymidine Phosphorylase*
Thymidine*
RNA
Thymidine
Thymidine Phosphorylase