Author of

• 30601

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  P2.01 - Advanced NSCLC (ID 159)

  • Event: WCLC 2019
  • Type: Poster Viewing in the Exhibit Hall
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall

  • 30651

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    P2.01-48 - Enhanced Expression of miR-204 Reduces Cisplatin Resistance in NSCLC  (ID 347)

    10:15 - 18:15  |  Presenting Author(s): Zhuo Cao
    • Abstract

    Background
    

    Non-small cell lung cancer (NSCLC) is the most common and lethal human malignant tumor worldwide. Platinum-based chemotherapy is still the mainstay treatment for NSCLC. However, long-term chemotherapy usually induces serious drug resistance. Accordingly, it is valuable to develop treatment strategies that could reduce the resistance against platinum-based drugsin NSCLC cells .

    Method
    

    Cisplatin-resistant NSCLC models in A549 and PC9 cell lines (CR-A549 and CR-PC9) were established through long-term exposure to cisplatin. Expression levels of caveolin-1 (CAV-1) and miR-204 in A549, PC9, CR-A549, and CR-PC9 cell lines were detected by western blot and q-PCR, respectively. Regulation of CAV-1 by miR-204 was assessed by bioinformatic analysis, western blot and luciferase reporter assay. The role of the miR-204/CAV-1 axis in regulating cisplatin resistance in NSCLC cells was tested by MTT assay. Interactions with Bcl-2-associated agonist of cell apoptosis (Bad) and Bcl-xl (Bcl-2) were evaluated by co-immunoprecipitation assay. Flow cytometry was used to detect the apoptosis of NSCLC cell lines.

    Result
    

    We observed significant upregulation of CAV-1 expression and a significant decrease of miR-204 expression in CR-A549 and CR-PC9 cells compared to their parental A549 and PC9 cells. Furthermore, we detected down regulation of miR cells. We then found that enforced expression of miR-204 can resensitize CR-A549 and CRPC9 cells to cisplatin treatment through the inhibition of CAV-1 expression. Thus, we declared that recovery of miR-204 expression was able to sensitize the cisplatin-induced mitochondrial apoptosis observed in CR-A549 and CR-PC9 cells through suppression of the caveolin-1/AKT/Bad pathway.

    Conclusion
    

    This study suggested that enhanced expression of miR-204 could increase the sensitivity of cisplatin treatment by suppression of caveolin-1/AKT/Bad pathway, which concluded that overexpression of miR-204 could be a potential approach for enhancing the sensitivity in NSCLC cells with cisplatin resistance.