NVP-BEZ235 Enhances Radiosensitivity of Human Prostate Cancer Cells but Acts as a Radioprotector to Normal Prostate Cells
| Autor: | John M. Akudugu, Mogammad Hamid, Antonio Serafin, Maleka S, Roswita Hamunyela, Daniel Achel |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Oncology
medicine.medical_specialty biology medicine.medical_treatment Cell medicine.disease Targeted therapy Prostate cancer medicine.anatomical_structure DU145 Internal medicine Cancer cell medicine Cancer research biology.protein Epidermal growth factor receptor PI3K/AKT/mTOR pathway EGFR inhibitors |
| Zdroj: | Journal of Cancer Biology and Therapeutics. 1 |
| ISSN: | 2379-5972 |
| DOI: | 10.18314/gjct.v1i1.32 |
| Popis: | Targeted therapy for prostate cancer may offer potential improvement over current conventional therapies because of its specificity. Although conventional treatments are effective, they are not always curative, andhave several limitations. In prostate cancer, activation of the epidermal growth factor receptor (EGFR) and the phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathways have been implicatedin tumorigenesis, and resistance to both conventional and targeted anticancer therapies. Single-target therapies may fail due to cellular heterogeneity. Concomitant targeting of EGFR and PI3K/mTOR cell signaling components may enhance the efficacy of radiotherapy. In this study, the effect of an EGFR inhibitor (AG-1478) and a dual inhibitor of PI3K and mTOR (NVP-BEZ235) on the radiation response of a human prostate carcinoma cell line (DU145) and a normal prostate cell line (1542N) was investigated, using the colony forming assay. Treatment ofDU145 cells with AG-1478 and NVP-BEZ235, either singly or in combination, resulted in a slight radiosensitisation of DU145 cells. Neither AG-1478 nor a cocktail of both inhibitors had an effect on the radiation response of the 1542N cell line. Interestingly, NVP-BEZ235 significantly protected 1542N cells from radiation-induced cell death. These data suggest that a specific inhibitor of PI3K and mTOR (NVP-BEZ235) could potentially be effective as a radio-protector. |
| Databáze: | OpenAIRE |
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