Author of

• 18502

  +

  P3.02c - Poster Session with Presenters Present (ID 472)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Advanced NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 18514

    +

    P3.02c-012 - Apatinib, a New Small Molecular VEGFR2 Inhibitor, Suppresses the Activity of Lung Cancer Stem Cells (ID 5836)

    14:30 - 14:30  |  Author(s): J. Zhu
    • Abstract

    Background:
    Cancer stem cells (CSCs) represent a small fraction of stem-like cells in the cancer that are characterized by their ability for self-renewal, proliferation, resistance to chemotherapy and radiation therapy, multipotent capability, and expression of stem cell markers. CSCs play essential role in cancer progression, chemoresistance, recurrence, and metastasis. Apatinib is a new small molecular VEGFR2 inhibitor which has been approved for the treatment of advanced or metastatic, chemo-refractory gastric cancer patients in China, and a phase II study evaluating its efficacy in patients with advanced NSCLC after second-line chemotherapy is currently ongoing. To date, however, no information is available regarding the action of Apatinib on CSCs. Therefore, the present study aimed to investigate the inhibitory effects of Aptinib on lung CSCs.
    
    Methods:
    Turmorsphere formation assay via serum-free medium (SFM) culturing was utilized to isolate and enrich lung CSCs from human lung cancer cell lines A549 and H1299. Protein and mRNA expression of lung CSCs markers, including CD133, CD44, ALDH1, Nanog, Sox2 and Oct4, was determined by Western blotting and qRT-PCR in sphere-forming A549 and H1299 cells. The number of CD133[+] cells was measured by Flow cytometry assay. Following the treatment of sphere-forming A549 and H1299 cells with Apatinib at various concentrations (0-10 µM), the inhibitory effects of Apatinib on lung CSCs were determined by tumorsphere formation, CSCs markers’ expression, number of CD133[+] cells, cell proliferation and apoptosis, activation of CSCs regulating signal pathways including Wnt/β-catenin and Sonic Hedgehog pathways, as well as the expression of VEGFR2 and ABC drug resistance proteins.
    
    Results:
    We revealed that sphere-forming A549 and H1299 cells in SFM culturing exhibited lung CSCs properties. Apatinib suppressed the sphere formation capacity of these cells in a concentration-dependent manner. The expression levels of lung CSCs markers and the number of CD133[+] cells were significantly downregulated by Apatinib. Our results further showed that Apatinib significantly inhibited the activation of Wnt/β-catenin and Sonic Hedgehog pathways, inhibited cell proliferation, and induced apoptosis in sphere-forming cells. Moreover, we demonstrated that Apatinib markedly reduced the expression levels of VEGFR2, as well as drug resistance proteins p-gp and ABCG2.
    
    Conclusion:
    Taken together, these data suggest for the first time the inhibitory effects of Apatinib on lung CSCs. Findings from this study could provide an important molecular basis for the application of Apatinib in chemo-refractory lung cancer patients.