Expression of Therapeutic Gene FCU1 Sensitizes Pancreatic Cancer Cells to 5-Fluorocytosine and Enhances the Cytotoxic Effect of 5-Fluorouracil

E P Kopantsev; M B Kostina; E V Grankina; M R Kopantseva; V I Egorov; E D Sverdlov

doi:10.1007/s10517-016-3517-9

Expression of Therapeutic Gene FCU1 Sensitizes Pancreatic Cancer Cells to 5-Fluorocytosine and Enhances the Cytotoxic Effect of 5-Fluorouracil

Bull Exp Biol Med. 2016 Oct;161(6):808-810. doi: 10.1007/s10517-016-3517-9. Epub 2016 Oct 26.

Authors

E P Kopantsev¹, M B Kostina², E V Grankina³, M R Kopantseva², V I Egorov⁴, E D Sverdlov²

Affiliations

¹ Laboratory of Structure and Functions of Human Genes, M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia. kopantzev@ibch.ru.
² Laboratory of Structure and Functions of Human Genes, M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
³ A. V. Vishnevsky Institute of Surgery, Ministry of the Health of the Russian Federation, Moscow, Russia.
⁴ Municipal Clinical Hospital No. 5, Moscow City Health Department, Moscow, Russia.

PMID: 27783293
DOI: 10.1007/s10517-016-3517-9

Abstract

Hybrid therapeutic gene FCU1 gene was cloned into a lentiviral expression vector and the therapeutic effect of its expression was studied in three pancreatic cancer cell lines. Expression of FCU1 gene sensitized cells of two of three studied pancreatic cancer cell lines to 5-fluorocytosine. In addition, uracil phosphoribosyl transferase activity of the hybrid FCU1 protein increased sensitivity of transfected cells of all three studied pancreatic cancer cell lines to 5-fluorouracil, a standard chemotherapeutic agent.

Keywords: 5-fluorocytosine; 5-fluorouracil; gene therapy; pancreatic cancer.

MeSH terms

Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cytosine Deaminase / genetics*
Cytosine Deaminase / metabolism
Drug Resistance, Neoplasm
Flucytosine / metabolism
Flucytosine / pharmacology
Fluorouracil / pharmacology
Gene Expression
Genetic Vectors / chemistry
Genetic Vectors / metabolism
Humans
Insulin-Secreting Cells / drug effects*
Insulin-Secreting Cells / metabolism
Insulin-Secreting Cells / pathology
Lentivirus / genetics
Lentivirus / metabolism
Pentosyltransferases / genetics*
Pentosyltransferases / metabolism
Plasmids / chemistry
Plasmids / metabolism
Recombinant Fusion Proteins / genetics*
Recombinant Fusion Proteins / metabolism
Transduction, Genetic

Substances

Antineoplastic Agents
Recombinant Fusion Proteins
Flucytosine
Pentosyltransferases
uracil phosphoribosyltransferase
Cytosine Deaminase
Fluorouracil