AI Article Synopsis
- Recent research shows that the PI3K/AKT and MEK/ERK pathways are regulated by the epidermal growth factor receptor in non-small cell lung cancer (NSCLC) and contribute to resistance against Gefitinib.
- In Gefitinib-sensitive cell lines, Gefitinib promotes cancer cell death by increasing the levels of a protein called BIM, and blocking BIM reduces this cell death.
- The combined use of PI3K and MEK inhibitors enhances apoptosis and restores sensitivity to Gefitinib, suggesting that combination therapy could be a strategy to tackle drug resistance in NSCLC.
Article Abstract
Recent evidence indicates that both the phosphatidylinositol 3-kinase (PI3K)/AKT and the MEK/ERK pathways are strictly regulated by epidermal growth factor receptor in non-small cell lung cancer (NSCLC) that responds to Gefitinib. Gefitinib resistance is partly owing to the activation of two major downstream signaling pathways PI3K/AKT or MEK/ERK. In this study, we found that in Gefitinib-sensitive cell lines, Gefitinib could induce tumor cell apoptosis via upregulation of a proapoptotic protein BIM. Small interfering RNA results showed that silencing of BIM could alleviate apoptosis induced by Gefitinib. We adopted a combination of PI3K inhibitor (LY294002) and MEK inhibitor (U0126) against Gefitinib resistance in cell lines. As expected, the combination substantially induced apoptosis and restored the sensitivity to Gefitinib by increasing the expression of BIM. Our studies provided a theoretical basis for overcoming drug resistance in NSCLC via combination therapy.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3589885 | PMC |
| http://dx.doi.org/10.1089/cbr.2012.1268 | DOI Listing |
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