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Ping Liu
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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
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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 | Presenting Author(s): Ping Liu
- Abstract
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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