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

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Title: Evaluating the immunoproteasome as a potential therapeutic target in cisplatin-resistant small cell and non-small cell lung cancer
Authors: Shoji, Tetsuaki Browse this author
Kikuchi, Eiki Browse this author →KAKEN DB
Kikuchi, Junko Browse this author
Takashima, Yuta Browse this author
Furuta, Megumi Browse this author
Takahashi, Hirofumi Browse this author
Tsuji, Kosuke Browse this author
Maeda, Makie Browse this author
Kinoshita, Ichiro Browse this author →KAKEN DB
Dosaka-Akita, Hirotoshi Browse this author →KAKEN DB
Sakakibara-Konishi, Jun Browse this author →KAKEN DB
Konno, Satoshi Browse this author →KAKEN DB
Keywords: Lung cancer
Cisplatin resistance
Immunoproteasome inhibitor
Cell cycle arrest
Issue Date: May-2020
Publisher: Springer
Journal Title: Cancer chemotherapy and pharmacology
Volume: 85
Start Page: 843
End Page: 853
Publisher DOI: 10.1007/s00280-020-04061-9
Abstract: 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.
Rights: This is a post-peer-review, pre-copyedit version of an article published in Cancer Chemotherapy and Pharmacology. The final authenticated version is available online at:
Type: article (author version)
Appears in Collections:北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 菊地 英毅

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