nsc-74859 and dactolisib

nsc-74859 has been researched along with dactolisib* in 1 studies

Other Studies

1 other study(ies) available for nsc-74859 and dactolisib

ArticleYear
Blockage of Stat3 enhances the sensitivity of NSCLC cells to PI3K/mTOR inhibition.
    Biochemical and biophysical research communications, 2014, Feb-21, Volume: 444, Issue:4

    The PI3K/Akt/mTOR axis in lung cancer is frequently activated and implicated in tumorigenesis. Specific targeting of this pathway is therefore an attractive therapeutic approach for lung cancer. However, non-small cell lung cancer cells are resistant to BEZ235, a dual inhibitor of PI3K and mTOR. Interestingly, blockage of Stat3 with a selective inhibitor, S3I-201, or siRNA dramatically sensitized the BEZ235-induced cell death, as evident from increased PARP cleavage. Furthermore, inhibition of Stat3 led to enhancement of cell death induced by LY294002, a PI3K inhibitor. Treatment of cells with a combination of BEZ235 and S3I-201 significantly induced the proapoptotic transcription factor, CHOP, and its targets, Bim and DR4. Knockdown of CHOP or Bim suppressed cell death stimulated by the combination treatment, implicating the involvement of these BEZ235/S3I-201-induced factors in pronounced cell death. Moreover, the BEZ235/S3I-201 combination enhanced TRAIL-induced cell death. Our results collectively suggest that blockage of Stat3 presents an effective strategy to overcome resistance to PI3K/Akt/mTOR inhibition.

    Topics: Aminosalicylic Acids; Antineoplastic Agents; Benzenesulfonates; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Drug Resistance, Neoplasm; Humans; Imidazoles; Lung; Lung Neoplasms; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Protein Kinase Inhibitors; Quinolines; RNA Interference; RNA, Small Interfering; Signal Transduction; STAT3 Transcription Factor; TOR Serine-Threonine Kinases

2014