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W.M. Li



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    MA17 - Genetic Drivers (ID 409)

    • Event: WCLC 2016
    • Type: Mini Oral Session
    • Track: Biology/Pathology
    • Presentations: 1
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      MA17.11 - Knockdown of Akt2 Suppresses Tumorigenesis and Raf1 Overexpression Offsets This Effect in Non-Small Cell Lung Cancer (ID 5462)

      14:20 - 15:50  |  Author(s): W.M. Li

      • Abstract
      • Presentation
      • Slides

      Background:
      Akt2 (Protein Kinase B isoform 2) is an essential protein, which is involved in tumor cell proliferation, differentiation, motility, and cell death in non small cell lung cancer (NSCLC). Raf1 is also a key protein regulating the functions in NSCLC. However, the relationships between Akt2 and Raf1 are unknown. This study aimed to investigate the influence of Akt2 knockdown and its interaction with overexpression Raf-1 in non-small cell lung cancer cells.

      Methods:
      Small interfering RNA was used to knockdown Akt2 and lentivirus was introduced to overexpress Raf1 in H1299, A549, Sk-mes and H460 cell lines. Western blot was performed to investigate expression levels of relevant proteins in the pathway. Cell survival, proliferation and apoptosis were evaluated in vitro and vivo. Then we examined Akt2 and Raf1 expressions via immunohistochemistry (IHC) in 65 NSCLC patients.

      Results:
      Knockdown of Akt2 suppressed cell proliferation, arrested tumor cells in G0/G1 phase and induced apoptosis in all cell lines distinctively. Raf1 phosphorylation was also inhibited after Akt2 knockdown in the cell lines. When Raf1 overexpression combined with Akt2 knockdown in these cell lines, cell proliferation was enhanced, and apoptosis rates was decrease compared with Akt2 knockdown alone. These trends were also observed in vivo experiments. Furthermore, the downstream proteins of Raf1, such as MEK, ERK, p-MEK and p-ERK were observed decrease in Akt2 knockdown groups. Of all NSCLC specimens, Akt2(+)/Raf1(+) patients had the worst prognosis of 5-year overall survivals. Figure 1



      Conclusion:
      Our study demonstrates that knockdown of Akt2 suppresses tumorigenesis by attenuating cell proliferation, increasing apoptosis and interfering cell cycle in non-small cell lung cancer. Raf1 overexpression partly offsets these effects by enhancing cell proliferation, suppressing apoptosis and affecting downstream proteins. Thus, there may be existing Akt2/Raf1 pathway in NSCLC, which plays an important role in tumorigenesis.

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