Author of

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  P1.03 - Biology (Not CME Accredited Session) (ID 935)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall

  • 26411

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    P1.03-15 - TMS Reduced Gefitinib Resistance In NSCLCs Via Suppressing MAPK/Akt/Bcl-2 Pathway by Upregulation of miR-345 and miR-498 (ID 11221)

    16:45 - 18:00  |  Author(s): Bin Liu
    • Abstract
    • Slides

    Background
    

    Despite initial dramatic efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs) in EGFR-mutant lung cancer patients, subseqent emergence of acquired resistance is almost inevitable. Resveratrol and its derivatives have been found to exert some effects on EGFR-TKI resistance in non-small cell lung cancer (NSCLC), but the underlying mechanisms remain unclear.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    We screened several NSCLC cell lines with gefitinib-resistance by MTT assay, and analyzed the miR-345/miR-498 expression levels. NSCLC cells were pre-treated with a resveratrol derivative, trans-3, 5, 4-trimethoxystilbene (TMS), and subsequently challenged with gefitinib treatment. The changes of apoptosis and miR-345/miR-498 expression were analyzed by flow cytometry and q-PCR, respectively. The functions of miR-345/miR-498 were verified by CCK-8 assay, cell cycle analysis, dual-luciferase reporter gene assay and immunoblotting analysis.

    4c3880bb027f159e801041b1021e88e8 Result
    

    Our results showed that the expression of miR-345 and miR-498 significantly decreased in gefitinib-resistant NSCLC cells. TMS pre-treatment significantly upregulated the expression of miR-345 and miR-498, increasing the sensitivity of NSCLC cells to gefitinib and inducing apoptosis. MiR-345 and miR-498 were verified to inhibit proliferation by cell cycle arrest, and regulate the MAPK/c-Fos and AKT/Bcl-2 signaling pathways by directly targeting MAPK1 and PIK3R1, respectively. The combination of TMS and gefitinib promoted apoptosis also by miR-345 and miR-498 targeting the MAPK/c-Fos and AKT/Bcl-2 signaling pathways.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Our study demonstrated that TMS reduced gefitinib resistance in NSCLCs via suppressing MAPK/Akt/Bcl-2 pathway by upregulation of miR-345/498. These findings would lay the theoretical basis for the future study of TMS for the treatment of EGFR-TKI resistance in NSCLCs.

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