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

Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine
Xi-Feng JinMichael Orth

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 γ-irradiation at doses of 0, 2, 4, or 6 Gy by colony formation assay. Somatostatin receptor type 2 (SSTR2) expression and 68Ga-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 68Ga-DOTATOC in NET cells. Conclusion: This preclinical study demonstrated that 5-fluorouracil alone or in combina...Continue Reading

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