A new putative target for antisense gene therapy of glioma: glycogen synthase.
The treatment of malignant brain gliomas remains a challenge, despite the availability of the classical triad of surgery, radiotherapy, and chemotherapy. There is thus the need for investigations into other forms of treatment strategies, such as gene therapy. Using antisense technology we have targeted glycogen metabolism, since malignant astrocytes present a high content of glycogen. In vitro rat C6‑glioma cells, transfected with antisense glycogen synthase (C6‑AS cells) exhibited a decreased expression of glycogen synthase and reduced activity of glycogen synthesis, along with attenuated invasiveness. In vivo tumors induced by C6‑AS cells in nude mice exhibited a significant reduction in tumor growth compared with controls. This reduction could be mediated by the induction of MCH‑I expression. The inhibition of glycogen synthesis by antisense glycogen synthase validates a putative target and a new approach for further study to advance the much‑needed efficacy of intervention strategies for malignant gliomas.
Ardourel
Maryvonne
M
Neurobiology Laboratory, Orleans, France.
Blin
Marion
M
Moret
Jean-Luc
JL
Dufour
Thierry
T
Duc
Huynh-Thien
HT
Trojan
Jerzy
J
Cloix
Jean-François
JF
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015316:Genetic Therapy; D005910:Glioma / Q000378:metabolism / Q000628:therapy*; D006006:Glycogen Synthase / Q000737:chemistry / Q000378:metabolism*; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D016372:RNA, Antisense / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000378:metabolism
D014408:Biomarkers, Tumor; D016372:RNA, Antisense; D006006:Glycogen Synthase; D017526:Receptor, IGF Type 1