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Inhibition of H-ras as a treatment for experimental brain C6 glioma
Eddie Perkins1, John Calvert, John A Lancon
1Department of Neurosurgery, University of Mississippi Medical Center, Jackson, MS, USA.
Abstract:
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.
Insights
Pretreating rats with diallyl disulfide (DADS) inhibited H-ras expression, reducing brain glioma size and extending lifespan. Post-tumor treatment with DADS showed no significant benefits.
Area of Science:
- Oncology
- Neuroscience
- Pharmacology
Background:
- The H-ras oncogene is crucial for brain tumor growth and presents a potential therapeutic target.
- Diallyl disulfide (DADS) is known to inhibit H-ras activity.
Purpose of the Study:
- To investigate the efficacy of diallyl disulfide (DADS) as a treatment for experimental brain glioma in a rat model.
- To evaluate the impact of DADS on H-ras expression, tumor size, neurological status, and lifespan.
Main Methods:
- C6 glioma cells were implanted into Sprague-Dawley rats.
- Rats were treated with DADS (33 micromol) either 7 days before or after tumor cell implantation.
- Control groups received soybean oil.
- Outcomes assessed included H-ras expression, tumor size, neurological status, and lifespan.
Main Results:
- Pretreatment with DADS significantly reduced tumor size (P<0.05), improved neurological status (P<0.05), and extended lifespan (P<0.05) compared to controls.
- DADS pretreatment significantly decreased H-ras expression in brain tumor tissue (P<0.05).
- Treatment with DADS after tumor implantation did not improve clinical status or lifespan.
Conclusions:
- Pretreatment with DADS effectively inhibits H-ras expression in experimental C6 glioma, leading to improved outcomes in rats.
- DADS shows potential as a preventative agent for brain glioma, but higher doses or more potent inhibitors may be needed for post-tumor treatment.