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Ichiro Kinoshita



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    P2.03 - Biology (ID 162)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Biology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.03-53 - Immunoproteasome as a Potential Therapeutic Target in Cisplatin-Resistant Small and Non-Small Cell Lung Cancer (ID 365)

      10:15 - 18:15  |  Author(s): Ichiro Kinoshita

      • Abstract
      • Slides

      Background

      Cisplatin resistance remains a major problem in the treatment of both non-small (NSCLC) and small cell lung cancer (SCLC). Cisplatin has been reported to cause DNA damages and oxidative stress leading to numerous changes in cell physiology in transcriptional and protein levels. Thus, cisplatin-resistant (CR) cancer cells could alter the proteasome expression to eliminate abnormal proteins induced by cisplatin. Here, we examined the status of proteasomes in CR lung cancer cells and whether proteasomes could be a therapeutic target to overcome cisplatin resistance in lung cancer.

      Method

      CR variants were established from three NSCLC cell lines (A549, H1299, and H1975) and two SCLC cell lines (SBC3 and SBC5) in our laboratory. The activity of 20S proteasome core enzyme, the expressions of proteasome subunits, and the sensitivity of immunoproteasome inhibitors, Carfilzomib (CFZ) and PR957, were examined in these CR cells.

      Result

      The CR cells showed higher activity of 20S proteasome core enzyme compared with the parent cell counterparts. Quantitative RT-PCR and Western blot analysis revealed that all of the five CR cells had significantly higher expressions of immunoproteasomes, including PSMB8 and PSMB9, while no remarkable changes were observed in the expressions of standard proteasomes. H1299 and SBC3 cells became more sensitive to CFZ and PR957 when acquiring resistance to cisplatin. CFZ induced cell cycle G2/M arrest and apoptosis in CR variants of H1299 and SBC3.

      Conclusion

      Immunoproteasome can be a therapeutic target in a portion of cisplatin-resistant both of NSCLC and SCLC.

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