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Reduced growth rate of dimethylhydrazine-induced colon tumors in rats
A Tsunoda1, M Shibusawa, Y Tsunoda
1Department of Surgery, Showa University School of Medicine, Tokyo, Japan.
Abstract:
alpha-Difluoromethylornithine (DFMO) treatment has been shown to modify carcinogenesis in many experimental tumor models, including breast, urinary bladder, and colon. This study was designed to determine whether DFMO treatment can inhibit tumor growth on chemical-induced colon cancer in rats. Effectiveness of DFMO in combination with mitomycin C (MMC) was also evaluated. Forty-two Sprague-Dawley rats received dimethylhydrazine (20 mg/kg) s.c. once weekly for 20 wk to induce colon cancer. Then a double-contrast barium enema was performed, and colon tumors were detected. The animals were divided into four groups that were subjected to the following treatment: none; DFMO alone; MMC alone; and a combination of DFMO plus MMC. After 5 wk of treatment, the barium enema was repeated. For the evaluation of treatment efficacy, tumor doubling time was adopted. The mean tumor doubling time in the control group was 20.7 +/- 9.1 days (SD). "Response" was judged as effective when tumor doubling time in treatment groups was more than 38.9 days, calculated from the mean + 2 SDs in the control group. Response rates in the DFMO, MMC, and DFMO plus MMC groups were 40.0%, 10.0%, and 82.3%, respectively. DFMO was a more effective inhibitor of tumor growth than MMC, and DFMO in combination with MMC resulted in a synergic diminution of tumor growth. The double-contrast barium enema is useful to observe sequential tumor growth and may be appropriate for the evaluation of new treatment on experimental colon cancer in rats.
Insights
Alpha-difluoromethylornithine (DFMO) effectively inhibits colon cancer growth in rats. Combining DFMO with mitomycin C (MMC) showed synergistic effects, significantly reducing tumor growth and demonstrating a high response rate.
Area of Science:
- Oncology
- Experimental Medicine
- Pharmacology
Background:
- Alpha-difluoromethylornithine (DFMO) has demonstrated anti-carcinogenic effects in various experimental tumor models.
- Colon cancer remains a significant health concern, necessitating novel therapeutic strategies.
Purpose of the Study:
- To evaluate the efficacy of DFMO in inhibiting tumor growth in a chemically induced rat colon cancer model.
- To assess the combined effectiveness of DFMO and mitomycin C (MMC) in treating colon cancer.
Main Methods:
- Colon cancer was induced in Sprague-Dawley rats using dimethylhydrazine.
- Tumor growth was monitored using double-contrast barium enemas.
- Animals were treated with either no treatment, DFMO alone, MMC alone, or a combination of DFMO and MMC.
- Tumor doubling time was used to evaluate treatment efficacy.
Main Results:
- DFMO alone showed a 40.0% response rate, while MMC alone had a 10.0% response rate.
- The combination of DFMO and MMC achieved an 82.3% response rate, indicating a synergistic effect.
- DFMO demonstrated superior tumor growth inhibition compared to MMC alone.
Conclusions:
- DFMO is an effective inhibitor of experimental colon cancer growth in rats.
- Combination therapy with DFMO and MMC offers a synergistic approach for diminishing tumor growth.
- Double-contrast barium enema is a valuable tool for monitoring tumor progression and evaluating treatment responses in preclinical colon cancer studies.
