Combination of 5-Fluorouracil with Epigenetic Modifiers Induces Radiosensitization, Somatostatin Receptor 2 Expression, and Radioligand Binding in Neuroendocrine Tumor Cells In Vitro

Jin, Xi-Feng; Auernhammer, Christoph J.; Ilhan, Harun; Lindner, Simon; Nolting, Svenja; Maurer, Julian; Spottl, Gerald und Orth, Michael (2019): Combination of 5-Fluorouracil with Epigenetic Modifiers Induces Radiosensitization, Somatostatin Receptor 2 Expression, and Radioligand Binding in Neuroendocrine Tumor Cells In Vitro. In: Journal of Nuclear Medicine, Bd. 60, Nr. 9: S. 1240-1246

Abstract

Peptide receptor radionuclide therapy in advanced neuroendocrine tumors (NETs) demonstrates a limited objective response rate. The therapeutic efficacy might be further increased by peptide receptor chemoradionuclide therapy. In this preclinical study, we explored the effects of 5-fluorouracil plus the DNA methyltransferase inhibitor decitabine or the histone deacetylase inhibitor tacedinaline on NET cells in vitro. Methods: Human NET cell lines BON1 and QGP1 were treated with 5-fluorouracil alone or in combination with decitabine or tacedinaline, respectively. Radiosensitivity was tested in combination with.-irradiation at doses of 0, 2, 4, or 6 Gy by colony formation assay. Somatostatin receptor type 2 (SSTR2) expression and Ga-68-DOTATOC uptake by human NET cell lines were investigated by Western blot analysis and by a radioligand binding assay. Results: Treatment with 5-fluorouracil alone or in combination with decitabine or tacedinaline reduced tumor cell viability and induced apoptosis, enhanced radiosensitivity in BON1 and QGP1 cells, induced SSTR2 expression, and resulted in increased radioligand binding of Ga-68-DOTATOC in NET cells. Conclusion: This preclinical study demonstrated that 5-fluorouracil alone or in combination with decitabine or tacedinaline caused radiosensitization of tumor cells, upregulation of SSTR2 expression in tumor cells, and increased radioligand binding of Ga-68-DOTATOC to these tumor cells. These preclinical in vitro findings indicate that 5-fluorouracil in combination with epigenetic modifiers might be a putative strategy to improve the treatment efficacy of peptide receptor chemoradionuclide therapy in NET.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0161-5505
• Sprache: Englisch