Author of

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  P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall

  • 26837

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    P2.01-41 - The Role and Mechanism Of FBW7 Deficiency in Advanced Non-Small Cell Lung Cancer with Docetaxel Resistance   (ID 11839)

    16:45 - 18:00  |  Presenting Author(s): Qisen Guo
    • Abstract

    Background
    

    Lung cancer is one of the most common malignant tumors of human. NSCLC accounts for about 80%-85% of all lung cancer, and 65%-80% of NSCLC patients have been diagnosed at the advanced stage^[1]. Because of the existence of drug resistance, many patients have relapsed or progressed soon after chemotherapy, and the resistance always lead to unsuccessful effect.

    Docetaxel is an anti-microtubule chemotherapeutic agent that acts on cellular tubulin, which can prevent the normal physiological accumulation of intracellular microtubules , resulting in the withering of cells^[2]. Like other chemotherapeutic drugs, the drug resistance of docetaxel reduces its efficacy.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    RT-PCR and Western-blot were used to detect the differences of FBW7 expression in docetaxel-resistant cell line SPC-A1/DTX and parental SPC-A1 cells, and the overexpression and interference sequences of FBW7 were constructed. The SPC-A1/DTX and parental SPC-A1 cells were transfected with lentiviral packaging, and the SPC-A1/DTX FBW7 O/E cell line and SPC-A1 FBW7 D/R cell line were screened by monoclonal screening method. RT-PCR and Western-blot were also used to detect the differences of FBW7 expression among SPC-A1/DTX, SPC-A1/DTX FBW7 O/E, SPC-A1 and SPC-A1 FBW7 D/R cell lines. Finally, MTT colorimetric assay and colony formation assay were used to research the effects of regulation of FBW7 on the sensitivity to docetaxel.

    4c3880bb027f159e801041b1021e88e8 Result
    

    RT-PCR and Western-blot proved that the expression of FBW7 in NSCLC docetaxel-resistant cell line SPC-A1/DTX was significantly lower than that of parental cell line SPC-A1. With lentiviral transfection and monoclonal screening, a SPC-A1 FBW7 D/R cell line with down-regulated FBW7 expression and an SPC-A1/DTX FBW7 O/E cell line with up-regulated FBW7 expression were constructed. The expression of FBW7 in SPC-A1 cell line and SPC-A1/DTX FBW7 O/E cell line was higher than that of SPC-A1/DTX FBW7 O/E cell line and SPC-A1 by RT-PCR and Western-blot. /DTX cell line. Finally, MTT colorimetric assay and colony formation assay showed that SPC-A1 cell line and SPC-A1/DTX FBW7 O/E cell line were more sensitive to docetaxel than SPC-A1 FBW7 D/R cell line and SPC-A1 /DTX cell line.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    For non-small cell lung cancer, the sensitivity to docetaxel was higher in cells with high expression of FBW7 than the cells with low expression of FBW7; the loss of FBW7 gene was associated with drug resistance of NSCLC to docetaxel. However, the specific mechanism of FBW7 deletion causing non-small cell lung cancer resistance to docetaxel still needs further study.

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