論文

査読有り 国際誌
2020年5月

Evaluating the immunoproteasome as a potential therapeutic target in cisplatin-resistant small cell and non-small cell lung cancer.

Cancer chemotherapy and pharmacology
  • Tetsuaki Shoji
  • ,
  • Eiki Kikuchi
  • ,
  • Junko Kikuchi
  • ,
  • Yuta Takashima
  • ,
  • Megumi Furuta
  • ,
  • Hirofumi Takahashi
  • ,
  • Kosuke Tsuji
  • ,
  • Makie Maeda
  • ,
  • Ichiro Kinoshita
  • ,
  • Hirotoshi Dosaka-Akita
  • ,
  • Jun Sakakibara-Konishi
  • ,
  • Satoshi Konno

85
5
開始ページ
843
終了ページ
853
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1007/s00280-020-04061-9

PURPOSE: We evaluated the expression of proteasome subunits to assess whether the proteasome could be a therapeutic target in cisplatin-resistant lung cancer cells. METHODS: Cisplatin-resistant (CR) variants were established from three non-small cell lung cancer (NSCLC) cell lines (A549, H1299, and H1975) and two small cell lung cancer (SCLC) cell lines (SBC3 and SBC5). The expression of proteasome subunits, the sensitivity to immunoproteasome inhibitors, and 20S proteasomal proteolytic activity were examined in the CR variants of the lung cancer cell lines. RESULTS: All five CR cell lines highly expressed one or both of the immunoproteasome subunit genes, PSMB8 and PSMB9, while no clear trend was observed in the expression of constitutive proteasome subunits. The CR cells expressed significantly higher levels of PSMB8 and PSMB9 proteins, as well. The CR variants of the H1299 and SBC3 cell lines were more sensitive to immunoproteasome inhibitors, and had significantly more proteasomal proteolytic activity than their parental counterparts. CONCLUSIONS: The immunoproteasome may be an effective therapeutic target in a subset of CR lung cancers. Proteasomal proteolytic activity may be a predictive marker for the efficacy of immunoproteasome inhibitors in cisplatin-resistant SCLC and NSCLC.

リンク情報
DOI
https://doi.org/10.1007/s00280-020-04061-9
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32232513

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