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Title: | Investigating novel methods for non-small cell lung cancer growth inhibition |
Authors: | Fenech, Kimberly (2021) |
Keywords: | Lungs -- Cancer Cancer cells Cell death |
Issue Date: | 2021 |
Citation: | Fenech, K. (2021). Investigating novel methods for non-small cell lung cancer growth inhibition (Bachelor's dissertation). |
Abstract: | Introduction: Lung cancer is the second leading cause of death in Malta where NSCLC accounts for 80-85% of all lung cancer cases. The PI3K/AKT/mTOR pathway is one of the most dysregulated cascades in NSCLC. Dual PI3K/mTOR inhibitors are able to inhibit PI3K, mTORC1 and mTORC2 completely shutting down the pathway, inhibiting cancer cell survival and proliferation. Aim: To sensitize large cell carcinoma (H460) cells, the most aggressive type of NSCLC using NVP-BEZ235, a dual PI3K/mTOR inhibitor. Methods: A PrestoBlue® viability assay was done to test the cytotoxicity of NVPBEZ235 at various concentrations on H460 cells. Then an ELISA was done to investigate if NVP-BEZ235 was able to block the PI3K/AKT/mTOR pathway by quantifying the protein levels of eIF4E, one of the proteins that is activated by mTORC1. Results: NVP-BEZ235 caused a concentration and time-dependant decrease in % cell viability. The ELISA showed that after just 5 hours of treatment with NVP-BEZ235 the concentration of eIF4E lysate had already decreased from 820 pg/ml (untreated) to 50 pg/ml. Conclusion: NVP-BEZ235 effectively inhibits cell proliferation in H460 cells. This is due to a reduction in free eIF4E which results from the inhibition of PI3K and mTORC1. A reduction in eIF4E limits the translation of growth-promoting proto-oncogenes resulting in cancer cell death. Future work: Both the viability assay and ELISA can be repeated on the other NSCLC cell lines to investigate the effect of the drug on other subtypes of NSCLC. A migration assay can also be done to test if NVP-BEZ235 can inhibit invasion and metastasis in NSCLC. |
Description: | B.Sc. (Hons) Med. Biochem.(Melit.) |
URI: | https://www.um.edu.mt/library/oar/handle/123456789/88317 |
Appears in Collections: | Dissertations - FacM&S - 2021 Dissertations - FacM&SPB - 2021 |
Files in This Item:
File | Description | Size | Format | |
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21BMB009.pdf Restricted Access | 2.27 MB | Adobe PDF | View/Open Request a copy |
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