OBJECTIVETo study the role of connexin gene (Cx43) in the suppression of C6 glioma.

METHODSCx43 gene depleted parental C6 rats (control group) and C6 cells transfected with Cx43 cDNA (transfection group) were implanted into the right caudate nucleus of SD rats. Rats bearing cerebral C6 gliomas were treated with Cx43 cDNA (treatment group) with another group treated with empty vector (empty vector group) serving as control. The general manifestation, survival time, MRI dynamic scanning and histopathological changes in all rats were observed. Cx43 mRNA and its protein were examined by in situ hybridization and immunohistochemistry. Proliferation activity was monitored by the average number of AgNOR stain. Cell apoptosis was examined by the Tolt-mediated x-duTP nick end labeling (TUNEL) method.

RESULTSAll rats in the control and empty vector groups died of cerebral glioma within 3 weeks after implantation of C6 cells. Six in the transfection group and 8 in the treatment group were alive beyond 120 days with complete disappearance of the tumor foci, except one in this group having some residue of tumor. In the glioma of transfection and treatment groups, Cx43 gene expression was up-regulated, proliferation activity reduced while the apoptotic cells did not increase.

CONCLUSIONThe development of glioma is greatly suppressed by the transfection of Cx43 gene, which has great effectiveness in rats bearing cerebral malignant gliomas. This could become a target of choice in the gene treatment of malignant gliomas.

Animals ; Brain Neoplasms ; mortality ; therapy ; Connexin 43 ; genetics ; therapeutic use ; Disease Models, Animal ; Genetic Therapy ; Glioma ; mortality ; therapy ; Male ; Neoplasm Transplantation ; Rats ; Rats, Sprague-Dawley ; Treatment Outcome