Academic Journal
Development and characterisation of a panel of phosphatidylinositide 3-kinase - mammalian target of rapamycin inhibitor resistant lung cancer cell lines.
| العنوان: | Development and characterisation of a panel of phosphatidylinositide 3-kinase - mammalian target of rapamycin inhibitor resistant lung cancer cell lines. |
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| المؤلفون: | Heavey, S, Dowling, P, Moore, G, Barr, MP, Kelly, N, Maher, SG, Cuffe, S, Finn, SP, O'Byrne, KJ, Gately, K |
| المصدر: | Sci Rep , 8 (1) , Article 1652. (2018) |
| سنة النشر: | 2018 |
| المجموعة: | University College London: UCL Discovery |
| مصطلحات موضوعية: | Cancer models, Cancer therapeutic resistance |
| الوصف: | The PI3K-mTOR pathway is involved in regulating all hallmarks of cancer, and is often dysregulated in NSCLC, making it an attractive therapeutic target in this setting. Acquired resistance to PI3K-mTOR inhibition is a major hurdle to overcome in the success of PI3K-mTOR targeted agents. H460, A549, and H1975 resistant cells were generated by prolonged treatment in culture with Apitolisib (GDC-0980), a dual PI3K-mTOR inhibitor over a period of several months, from age-matched parent cells. Resistance was deemed to have developed when a log fold difference in IC50 had been achieved. Resistant cell lines also exhibited resistance to another widely investigated PI3K-mTOR dual inhibitor; Dactolisib (BEZ235). Cell lines were characterised at the level of mRNA (expression array profiling expression of >150 genes), miRNA (expression array profiling of 2100 miRNAs), protein (bottoms-up label-free mass spectrometry) and phosphoprotein (expression array profiling of 84 phospho/total proteins). Key alterations were validated by qPCR and Western blot. H1975 cells were initially most sensitive to Apitolisib (GDC-0980), but developed resistance more quickly than the other cell lines, perhaps due to increased selective pressure from the impressive initial effect. In-depth molecular profiling suggested epithelial-mesenchymal transition (EMT) may play a role in resistance to PI3K-mTOR dual inhibition in NSCLC. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| Relation: | https://discovery.ucl.ac.uk/id/eprint/10043252/1/s41598-018-19688-1.pdf; https://discovery.ucl.ac.uk/id/eprint/10043252/ |
| الاتاحة: | https://discovery.ucl.ac.uk/id/eprint/10043252/1/s41598-018-19688-1.pdf https://discovery.ucl.ac.uk/id/eprint/10043252/ |
| Rights: | open |
| رقم الانضمام: | edsbas.2915FF82 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |