期刊
PANCREAS
卷 33, 期 2, 页码 142-147出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/01.mpa.0000226882.48204.26
关键词
uracil-tegafur; 5-fluorouracil; gemcitabine; human equilibrative nucleoside transporter; combination chemotherapy; pancreatic cancer
Objectives: Gemcitabine is taken up by cells mainly via human equilibrative nucleoside transporter I (hENT1). Pretreatment of cancer cell lines with 5-fluorouracil (5-FU) leads to an increase in the expression of hENT1 and augments the effect of single-agent gemcitabine treatment in vitro. The purpose of the present study was to evaluate the relationship between the schedules of gemcitabine/uracil-tegafur (UFT) combination therapy and their effects in pancreatic cancer in vivo. Methods: The expression level of hENT1 mRNA was examined using 6 types of human pancreatic cancer cell lines treated with 5-FU and MiaPaCa-2 xenograft tumors in BALB/c nu/nu mice treated with UFT. A [H-3] gemcitabine cellular uptake assay was performed using MiaPaCa-2 cells treated with 5-FU. We compared the effects of 6 different schedules of treatment using UFT and/or gemcitabine on MiaPaCa-2 xenograft tumors. Results: MiaPaCa-2 cell line was one of the lines that showed the highest rate of 5-FU-induced increase in the hENT1 mRNA level. Gemcitabine uptake was significantly increased when cells were treated with 5-FU. Treatment with UFT significantly increased the hENT1 mRNA expression in MiaPaCa-2 tumors. A significant growth inhibition of MiaPaCa-2 tumors was observed in the mice treated with UFT followed by gemcitabine as compared with either untreated mice or UFT alone-treated mice. Conclusions: Our results suggest that the schedule in which the gemcitabine is administered after UFT may be the optimal combination for gemcitabine/UFT treatment in pancreatic cancer.
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