論文

査読有り 国際誌
2017年9月

Proteasome Inhibitor-Loaded Micelles Enhance Antitumor Activity Through Macrophage Reprogramming by NF-κB Inhibition.

Journal of pharmaceutical sciences
  • Hailiang Wu
  • ,
  • Anqi Tao
  • ,
  • John D Martin
  • ,
  • Sabina Quader
  • ,
  • Xueying Liu
  • ,
  • Kei Takahashi
  • ,
  • Louise Hespel
  • ,
  • Yutaka Miura
  • ,
  • Yoshihiro Hayakawa
  • ,
  • Tatsuro Irimura
  • ,
  • Horacio Cabral
  • ,
  • Kazunori Kataoka

106
9
開始ページ
2438
終了ページ
2446
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.xphs.2017.03.031

Macrophage reprogramming toward a tumor-attacking phenotype is a promising treatment strategy, yet such strategies are scarce and it is not clear how to combine them with cytotoxic therapies that are often used to treat solid tumors. Here, we evaluate whether a micelle-encapsulated proteasome inhibitor, that is, the peptide aldehyde drug MG132, which is cytotoxic to cancer cells, can reprogram macrophages to attack the tumor. Through in vitro studies, we demonstrated that the proteasome inhibition reduces nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling-a known promoter of tumor-supporting macrophages and chemoresistance-in both cancer cells and macrophages. In in vivo studies, we showed that, although free MG132 did not affect the macrophage phenotype in tumors even at its maximum tolerated dose, the micellar formulation of MG132 safely achieved simultaneous cancer cell killing and macrophage reprogramming, thereby enhancing the antitumor efficacy in a syngeneic, orthotopic breast cancer model.

リンク情報
DOI
https://doi.org/10.1016/j.xphs.2017.03.031
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28412401
ID情報
  • DOI : 10.1016/j.xphs.2017.03.031
  • PubMed ID : 28412401

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