Protein-bound polysaccharide-K augments the anticancer effect of fluoropyrimidine derivatives possibly by lowering dihydropyrimidine dehydrogenase expression in gastrointestinal cancers

  • Authors:
    • Eiji Mekata
    • Satoshi Murata
    • Hiromichi Sonoda
    • Tomoharu Shimizu
    • Tomoko Umeda
    • Hisanori Shiomi
    • Shigeyuki Naka
    • Hiroshi Yamamoto
    • Hajime Abe
    • Takeo Edamatsu
    • Ayako Fujieda
    • Masaki Fujioka
    • Tsutomu Wada
    • Tohru Tani
  • View Affiliations

  • Published online on: October 4, 2013     https://doi.org/10.3892/or.2013.2788
  • Pages: 2845-2851
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Abstract

Protein-bound polysaccharide-K (PSK) enhances the antitumor effect of anticancer drug when used clinically in combination with such drugs. PSK is known to act by immune-mediated mechanisms; however, the relationship between PSK and metabolic enzymes of anticancer drugs is unknown. We used the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) clinically to evaluate the sensitivity of anticancer drugs. In the present study, we modified the CD-DST by adding peripheral blood mononuclear cells (PBMCs) (immuno-CD-DST) and examined the antitumor effect of PSK in combination with anticancer drugs. First, HCT116 human colon cancer cells were cultured with PSK and 5-fluorouracil (5-FU) or 5'-deoxy-5-fluorouridine (5'-DFUR) in the presence or absence of PBMCs, and the antiproliferative effects were compared. In the presence of PBMCs, PSK augmented the inhibitory effects of 5-FU and 5'-DFUR on HCT116 cell proliferation. Next, using human gastric cancer and colon cancer cell lines, the effects of PSK on mRNA expression of various metabolic enzymes of fluoropyrimidines: dihydropyrimidine dehydrogenase (DPD), thymidylate synthase, thymidine phosphorylase and orotate phosphoribosyl transferase, were examined by real-time PCR. PSK significantly enhanced DPD mRNA expression in all of the cancer cell lines tested, but not those of the other enzymes. Addition of IFN-α and TRAIL, cytokines known to inhibit DPD expression, to the cultures reduced DPD mRNA expression in the cancer cells. When PBMC samples collected from healthy volunteers were cultured with PSK, IFN-α mRNA expression increased in 3 of the 5 PBMC samples, while TRAIL mRNA expression was unchanged. The present results propose the possibility that PSK induces PBMCs to express IFN-α which inhibits DPD expression, and consequently augments the antitumor effect of 5-FU or 5'-DFUR. Immuno-CD-DST is useful for evaluating drugs with immunological mechanisms of action.
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December 2013
Volume 30 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Mekata E, Murata S, Sonoda H, Shimizu T, Umeda T, Shiomi H, Naka S, Yamamoto H, Abe H, Edamatsu T, Edamatsu T, et al: Protein-bound polysaccharide-K augments the anticancer effect of fluoropyrimidine derivatives possibly by lowering dihydropyrimidine dehydrogenase expression in gastrointestinal cancers. Oncol Rep 30: 2845-2851, 2013
APA
Mekata, E., Murata, S., Sonoda, H., Shimizu, T., Umeda, T., Shiomi, H. ... Tani, T. (2013). Protein-bound polysaccharide-K augments the anticancer effect of fluoropyrimidine derivatives possibly by lowering dihydropyrimidine dehydrogenase expression in gastrointestinal cancers. Oncology Reports, 30, 2845-2851. https://doi.org/10.3892/or.2013.2788
MLA
Mekata, E., Murata, S., Sonoda, H., Shimizu, T., Umeda, T., Shiomi, H., Naka, S., Yamamoto, H., Abe, H., Edamatsu, T., Fujieda, A., Fujioka, M., Wada, T., Tani, T."Protein-bound polysaccharide-K augments the anticancer effect of fluoropyrimidine derivatives possibly by lowering dihydropyrimidine dehydrogenase expression in gastrointestinal cancers". Oncology Reports 30.6 (2013): 2845-2851.
Chicago
Mekata, E., Murata, S., Sonoda, H., Shimizu, T., Umeda, T., Shiomi, H., Naka, S., Yamamoto, H., Abe, H., Edamatsu, T., Fujieda, A., Fujioka, M., Wada, T., Tani, T."Protein-bound polysaccharide-K augments the anticancer effect of fluoropyrimidine derivatives possibly by lowering dihydropyrimidine dehydrogenase expression in gastrointestinal cancers". Oncology Reports 30, no. 6 (2013): 2845-2851. https://doi.org/10.3892/or.2013.2788