YC-1 sensitizes the antitumor effects of boron neutron capture therapy in hypoxic tumor cells

Takaomi Harada, Katsumi Hirose, Yuki Wada, Mariko Sato, Koji Ichise, Masahiko Aoki, Takahiro Kato, Ken Takeda, Yoshihiro Takai

研究成果: Article査読

2 被引用数 (Scopus)

抄録

The uptake of boron into tumor cells is a key factor in the biological effects of boron neutron capture therapy (BNCT). The uptake of boron agents is suppressed in hypoxic conditions, but themechanism of hypoxia-inducedmodulation of suppression of boron uptake is not clear. Therefore, we evaluated whether hypoxia-inducible factor 1α (HIF-1α) contributes to attenuation of the antitumor effects of BNCT in hypoxic tumor cells.We also tested whether YC-1, a HIF-1α-targeting inhibitor, has therapeutic potential with BNCT. To elucidate the mechanism of attenuation of the effects of BNCT caused by hypoxia, deferoxamine (DFO) was used in experiments. Cells were incubated in normal oxygen, hypoxic conditions (1% O2) or 5 μM DFO for 24 h. Then, cells were treated with 10B-boronophenylalanine (BPA) for 2 h and boron accumulation in cells was evaluated. To clarify the relationship between HIF-1α and Ltype amino acid transporter 1 (LAT1), gene expression was evaluated by a usingHIF-1α gene knockdown technique. Finally, to improve attenuation of the effects ofBNCTin hypoxic cells,BNCTwas combinedwithYC-1. Boron uptake was continuously suppressed up to 2 h after administration of BPA by 5 μM DFO treatment. In cells treated with 5 μMDFO, LAT1 expression was restored inHIF-1α-knocked down samples in all cell lines, revealing that HIF-1α suppresses LAT1 expression in hypoxic cells. From the results of the surviving fraction after BNCT combined with YC-1, treatment with YC-1 sensitized the antitumor effects of BNCT in cells cultured in hypoxia.

本文言語English
ページ(範囲)524-534
ページ数11
ジャーナルJournal of radiation research
61
4
DOI
出版ステータスPublished - 2020 7 1

ASJC Scopus subject areas

  • 放射線
  • 放射線学、核医学およびイメージング
  • 健康、毒物学および変異誘発

フィンガープリント

「YC-1 sensitizes the antitumor effects of boron neutron capture therapy in hypoxic tumor cells」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル