Folylpolyglutamate synthase and γ-glutamyl hydrolase regulate leucovorin-enhanced 5-fluorouracil anticancer activity

Etsuko Sakamoto, Sayaka Tsukioka, Shinji Oie, Takashi Kobunai, Hiroaki Tsujimoto, Kazuki Sakamoto, Yoshihiro Okayama, Yoshikazu Sugimoto, Toshinori Oka, Masakazu Fukushima, Tatsuzo Oka

研究成果: Article査読

25 被引用数 (Scopus)

抄録

Although 5-fluorouracil (5-FU) plus leucovorin (LV) is a standard chemotherapy regimen for colorectal cancer, the factors that determine the LV-mediated enhancement of the antitumor activity of 5-FU have remained unknown. We investigated the roles of folylpolyglutamate synthase (FPGS) and γ-glutamyl hydrolase (GGH), which are the main enzymes involved in folate metabolism, in the effect of LV. LV enhanced the anticancer activity of 5-FU and the level of reduced folate in human colon cancer cells. Small-interfering RNA (siRNA) transfected into DLD-1 cells to downregulate FPGS reduced the basal level of reduced folate, the folate level after LV treatment, and the enhancement of 5-fluoro-2′-deoxyuridine (FdUrd)-induced cytotoxicity elicited by LV. By contrast, the downregulation of GGH by siRNA increased cellular sensitivity to FdUrd combined with LV. These results suggest that FPGS and GGH expression levels in tumors are determinants of the efficacy of LV in enhancing the antitumor activity of 5-FU.

本文言語English
ページ(範囲)801-807
ページ数7
ジャーナルBiochemical and Biophysical Research Communications
365
4
DOI
出版ステータスPublished - 2008 1 25
外部発表はい

ASJC Scopus subject areas

  • 生物理学
  • 生化学
  • 分子生物学
  • 細胞生物学

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