Side populations of glioblastoma cells are less sensitive to HSV-TK/GCV suicide gene therapy system than the non-side population.
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.
Hu
Weiwei
W
Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88 Jiefang Road, Hangzhou, 310009, China, huwwzju@163.com
Liu
Weiguo
W
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000998:Antiviral Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D015774:Ganciclovir / Q000627:therapeutic use*; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D005909:Glioblastoma / Q000235:genetics / Q000628:therapy*; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism; D018139:Simplexvirus / Q000235:genetics* / Q000378:metabolism; D013778:Tetrazolium Salts / Q000737:chemistry; D013844:Thiazoles / Q000737:chemistry; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism*
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000998:Antiviral Agents; D009363:Neoplasm Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; C070380:3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium; D013937:Thymidine Kinase; D015774:Ganciclovir