Inhibition of H-ras as a treatment for experimental brain C6 glioma.
The oncogene H-ras plays an important role in tumor growth and maintenance and could serve as a target treatment for brain tumors. In this study, diallyl disulfide (DADS), an inhibitor of H-ras was used to treat experimental brain glioma in a rat model. One hundred and twenty-five Sprague-Dawley rats (175-200 g) were implanted with 2 x 10(5) C6 glioma cells into the intra striatal region of the brain. Animals were treated with DADS (33 micromol) either before or after implantation of tumor cells. Control animals received soybean oil. Treatment outcome was evaluated based on H-ras expression in tumor tissue, animal's neurological status, tumor size, and life span. Application of DADS 7 days before implantation of tumor cells reduced the tumor size (P<0.05), improved neurological status (P<0.05), and increased the animal life span (P<0.05) when compared to the control group (no treatment). The expression of H-ras was significantly (P<0.05) reduced in brain tumor tissue of animals treated with DADS before implantation. Application of DADS after tumor implantation failed to improve clinical status or life span. This study demonstrates that pretreatment with DADS is capable of inhibiting the expression of H-ras in experimental brain C6 glioma which leads to an improved neurological status and an extended life span in the rat. Higher doses of DADS or other more potent inhibitors need to be used after tumor has been implanted.
Perkins
Eddie
E
Department of Neurosurgery, University of Mississippi Medical Center, Jackson, MS, USA.
Calvert
John
J
Lancon
John A
JA
Parent
Andrew D
AD
Zhang
John
J
D000498:Allyl Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D016380:Brain Tissue Transplantation; D004195:Disease Models, Animal; D004220:Disulfides / Q000494:pharmacology* / Q000627:therapeutic use; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D011905:Genes, ras / Q000187:drug effects* / Q000235:genetics; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism / Q000637:transplantation
D000498:Allyl Compounds; D000970:Antineoplastic Agents; D004220:Disulfides; C028009:diallyl disulfide