Antitumor effect of IL-2, p53, and bax gene transfer in C6 glioma cells.
The use of interleukin-2 (IL-2) and p53 for immunotherapy and gene therapy for cancer has shown promising results. In this study, we examined the efficacy of plasmid gene therapy utilizing murine IL-2, the wild-type (wt) human p53 gene, the combination of these genes, and the murine bax gene, which are under the control of the cytomegalovirus (CMV) immediate-early promoter, in nude mice bearing established subcutaneous C6 glioma. In vitro assays and immunocytochemical analysis for therapeutic genes demonstrated expression of the proteins in C6 transfected cells. In animal studies, significant antitumor activity was observed for the IL-2, p53/IL-2, and bax treated groups. However, no synergistic effect was observed in the p53/IL-2 combination group. Demonstrating for the first time, bax showed a significant reduction of tumor volume when compared to p53 (p < 0.02). Thus, our in vivo studies show that delivery of naked therapeutic genes is safe and results in significantly slower progression of glioma in athymic rodents.
Center for Molecular Biology and Gene Therapy, Loma Linda University School of Medicine, CA 92350, USA.
P
P
Haghighat
T M
TM
Timiryasova
B
B
Chen
E H
EH
Kajioka
D S
DS
Gridley
I
I
Fodor
D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005910:Glioma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D007167:Immunotherapy; D007376:Interleukin-2 / Q000235:genetics / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000627:therapeutic use*; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; C494828:Bax protein, rat; D007376:Interleukin-2; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein