Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Schneider, R; Gademann, G; Ochel, HJ; Neumann, K; Jandrig, B; Hass, P; Walke, M; Schostak, M; Brunner, T; Christoph, F.
Functional and mutational analysis after radiation and cetuximab treatment on prostate carcinoma cell line DU145.
Radiat Oncol. 2021; 16(1): 137
Doi: 10.1186/s13014-021-01859-6
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Brunner Thomas Baptist
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- BACKGROUND: Epidermal Growth Factor Receptor is often overexpressed in advanced prostate carcinoma. In-vitro-studies in prostate carcinoma cell line DU145 have demonstrated increased sensibility to radiation after cetuximab treatment, but clinical data are not sufficient to date. METHODS: We analyzed effects of radiation and cetuximab in DU145 and A431 using proliferation, colony-forming-unit- and annexin-V-apoptosis-assays. Changes in protein expression of pEGFR and pERK1/2 after radiation and cetuximab treatment were analyzed. Using NGS we also investigated the impact of cetuximab long-term treatment. RESULTS: Cell counts in DU145 were reduced by 44% after 4 Gy (p = 0.006) and 55% after 4 Gy and cetuximab (p < 0.001). The surviving fraction (SF) was 0.69 after 2 Gy, 0.41 after 4 Gy and 0.15 after 6 Gy (each p < 0.001). Cetuximab treatment did not alter significantly growth reduction in 4 Gy radiated DU145 cells, p > 0.05 or SF, p > 0.05, but minor effects on apoptotic cell fraction in DU145 were detected. Using western blot, there were no detectable pEGFR and pERK1/2 protein signals after cetuximab treatment. No RAS mutation or HER2 amplification was detected, however a TP53 gen-mutation c.820G > T was found. CONCLUSIONS: Radiation inhibits cell-proliferation and colony-growth and induces apoptosis in DU145. Despite blocking MAP-Kinase-pathway using cetuximab, no significant radiation-sensitizing-effect was detected. Cetuximab treatment did not induce resistance-mutations. Further research must clarify which combination of anti-EGFR treatment strategies can increase radiation-sensitizing-effects.
- Find related publications in this database (using NLM MeSH Indexing)
- Antineoplastic Agents, Immunological - pharmacology
- Apoptosis - administration & dosage
- Biomarkers, Tumor - genetics
- Cell Proliferation - administration & dosage
- Cetuximab - pharmacology
- Chemoradiotherapy - methods
- Gene Expression Regulation, Neoplastic - administration & dosage
- Humans - administration & dosage
- Male - administration & dosage
- Mutation - administration & dosage
- Prostatic Neoplasms - genetics, pathology, therapy
- Radiation Dosage - administration & dosage
- Radiation-Sensitizing Agents - pharmacology
- Tumor Cells, Cultured - administration & dosage
- Find related publications in this database (Keywords)
- Cetuximab
- Radiation
- DU145
- Prostate cancer
- Surviving fraction
- Resistance mutations