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X. Li



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    P3.05 - Poster Session with Presenters Present (ID 475)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Palliative Care/Ethics
    • Presentations: 1
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      P3.05-016 - Mitochondial Pathway Mediated Apoptosis is Involved in Erlotinib-Induced Cytoxicity in Hepatic Cells (ID 4299)

      14:30 - 14:30  |  Author(s): X. Li

      • Abstract
      • Slides

      Background:
      For advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor(EGFR) mutations, EGFR tyrosine kinase inhibitors(TKIs) including erlotinib are indicated for the first-line treatment. Liver injury is one of many limited toxicities of erlotinib and can greatly affect its safety. This study explored the mechanism of erlotinib-induced hepatotoxicity in vitro and provide experimental evidence for screening potential hepatoprotectors.

      Methods:
      L02 cells, human hepatocytes were cultured for investigating mechanism of erlotinib-induced hepatotoxicity in vitro. The cell inhibition rate was detected by sulforhodamine B (SRB) colorimetric assay and IC50 value was calculated. Apoptosis was evaluated by DAPI staining and Annexin V-FITC/PI staining for flow cytometry, moreover, the variation of mitochondrial membrane potential (△Ψm) was examined using JC-1 staining. The expressions of apoptosis related protein including cleavage of poly-ADP-ribose polymerase (PARP), c-caspase-3, Bcl-2 and Bax were detected with West blotting.

      Results:
      We found that erlotinib induced dose-dependent cytotoxicity in human L02 hepatic cells 72 h after treatment. In other experiments, L02 cells were treated with erlotinib for 48 h and displayed typical features of apoptosis. Erlotinib caused alteration of nucleus morphology such as chromatin condensation and karyopyknosis. It also induced a raise in the fraction of late apoptotic cells and regulation of apoptosis protein expression including activation of c-caspase-3 as well as c-PARP. Furthermore, 48 h exposure to erlotinib disturbed mitochondrial functions by reducing both the ratio of Bcl-2 to Bax proteins and mitochondrial membrane potential.

      Conclusion:
      The results of this in vitro study suggested that erlotinib-induced hepatotoxicity may occur through mitochondrial-pathway mediated apoptosis.

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