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M. A. Aswisi
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P2.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 225)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.08-014 - Therapeutic Effectiveness of MET/RON Small Molecule Inhibitor BMS-777607 on Cell Viability of Human Malignant Pleural Mesothelioma Cell Lines (ID 2832)
09:30 - 09:30 | Author(s): M. A. Aswisi
- Abstract
Background:
Overexpression of c-Met receptor tyrosine kinase has been highly associated with oncogenic progression of non-neoplastic mesothelial progenitor cells to malignant pleural mesothelioma (MPM). Moreover, activated c-Met receptor tyrosine kinase transduces signals that regulate tumorigenic activities including cell growth, migration, survival, and invasion of extracellular matrixes. A small molecule MET kinase inhibitor (BMS-777607) is an inhibitor of tyrosine receptor currently under clinical trials. Previous studies reported the effect of this inhibitor on cancer cells such as breast, hepatic and prostate cancer. However, its inhibitory effect on malignant pleural mesothelioma (MPM) cells has not yet been evaluated. In our study, we aimed to investigate the therapeutic usefulness of this small molecule on MPM.
Methods:
Human MPM cell lines such as REN and NCl-H2373 and a human lung carcinoma cell line (NCl-H226) were used. LP-9 cell line, which resembles normal human mesothelial cells, was used as control. These cells were cultured and exposed to BMS-777607 at concentrations 1uM, 5uM and 10uM. Cell cycle, cell viability, lysosomal mass/pH changes and mitochondrial membrane potential were examined using immunofluorescent staining methods and data were collected and analysed with high content screening systems such as Cytell and IN Cell Investigator software.
Results:
Both MPM cell lines and the lung cell line showed cell cycle arrest as examined by Cytell in significant dose-dependent manner with maximum effects seen at the highest dose (10 µM) of BMS-777607. Cell viability and other biological cellular markers were also altered upon exposure to this small molecule. Our results showed that BMS-777607 induces negligible changes of these markers examined in the normal mesothelial cells line (LP-9).
Conclusion:
Taken together, these findings indicate that inhibition of MET/RON signalling using a small molecule inhibitor such as BMS-777607 could significantly interrupt the cell cycle stages and alter other cellular compartments (i.e; lysosomal mass/pH, mitochondrial membrane potential) which lead to suppression of MPM cell viability, suggesting that such a targeting strategy may hold promise for the treatment of MPM.
