Author of

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  P69 - Tumor Biology and Systems Biology - Basic and Translational Science - RTK/EGFR (ID 208)

  • Event: WCLC 2020
  • Type: Posters
  • Track: Tumor Biology and Systems Biology - Basic and Translational Science
  • Presentations: 1
  • Moderators:
  • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall

  • 35885

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    P69.04 - Reduction of Drug Resistance Through Calcium Control in EGFR TKI  Resistant Lung Cancer Cells (ID 2144)

    00:00 - 00:00  |  Presenting Author(s): Sei-hoon Yang
    • Abstract
    • Slides

    Introduction
    

    Despite the development of various anticancer drugs, anticancer drug resistance from prolonged drug exposure is a major obstacle to cancer treatment. It has been reported that changes in intracellular calcium signals are observed in tumorigenesis. However, the association between anticancer drug resistance and abnormal calcium signaling mechanisms in Non-small cell lung cancer (NSCLC) is not fully understood. The aim of this study is to investigate the relationship between calcium and anticancer activity by observing and controlling altered calcium signals in gefitinib-resistance NSCLC cells and to suggest a fundamental solution to overcome acquired resistance.

    Methods
    

    We analyzed the intracellular calcium ([Ca²⁺]i) signals in PC-9 cells and PC-9/GR (Gefitinib Resistant) cells under following conditions. We observed hEGF (200ng/ml)-mediated [Ca²⁺]i oscillations response. Calcium influx, endoplasmic reticulum (ER) calcium contents, hEGF (200 ng/ml)-mediated [Ca²⁺]i oscillations, and effects of inhibitors were studied in absence of extracellular calcium ([Ca²⁺]e). We compared gefitinib-induced cytotoxicity and cell viability according to the presence or absence of [Ca²⁺]e.

    Results
    

    In PC-9/GR cells, hEGF (200 ng/ml)-mediated [Ca²⁺]i oscillations response did not occurred and basal level was up-regulated by spontaneous store-operated Ca²⁺ entry (SOCE). ER Ca²⁺ contents were lower in PC-9/GR cells (0.014 ± 0.007) compare to PC-9 cells (1.382 ± 0.028). SOCE is continuously activated in PC-9/GR cells by maintaining of depletion from ER calcium contents to mediated extracellular calcium influx. EGF-mediated [Ca²⁺]i oscillations evoked in absence of [Ca²⁺]e both PC-9 cell and PC-9/GR cells. The effects were blocked by U73122, PLC inhibitor, and gefitinib, EGFR-TKI. Also removal of [Ca²⁺]e increased synergistically gefitinib-induced cytotoxicity and cell viability.

    Conclusion
    

    Extracellular calcium is involved in reducing acquired drug resistance of EGFR TKI. .

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