Abstract
Side populations of glioblastoma cells are resistant to chemotherapy basically due to ABCG2-mediated efflux of small-molecule drugs. The herpes simplex virus thymidine kinase/ganciclovir suicide gene therapy system is one of the best-characterized strategies for malignant tumors including glioblastoma. Since this system involves a small-molecule drug ganciclovir, we wonder if glioblastoma side population cells are able to "pump out" ganciclovir and thus resistant to this suicide gene therapy. By 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, we found that side populations are more resistant to this system than non-side populations. By flow cytometry and competition assay, we found that ganciclovir is a substrate for ABCG2.
MeSH terms
-
ATP Binding Cassette Transporter, Subfamily G, Member 2
-
ATP-Binding Cassette Transporters / metabolism
-
Antiviral Agents / therapeutic use*
-
Cell Line, Tumor
-
Flow Cytometry
-
Ganciclovir / therapeutic use*
-
Genes, Transgenic, Suicide
-
Genetic Therapy / methods*
-
Genetic Vectors / genetics
-
Genetic Vectors / metabolism
-
Glioblastoma / genetics
-
Glioblastoma / therapy*
-
Humans
-
Neoplasm Proteins / metabolism
-
Simplexvirus / genetics*
-
Simplexvirus / metabolism
-
Tetrazolium Salts / chemistry
-
Thiazoles / chemistry
-
Thymidine Kinase / genetics
-
Thymidine Kinase / metabolism*
Substances
-
ABCG2 protein, human
-
ATP Binding Cassette Transporter, Subfamily G, Member 2
-
ATP-Binding Cassette Transporters
-
Antiviral Agents
-
Neoplasm Proteins
-
Tetrazolium Salts
-
Thiazoles
-
3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium
-
Thymidine Kinase
-
Ganciclovir