Tsunoda A, Shibusawa M, Tsunoda Y, Yasuda N, Koike T
Department of Surgery, Showa University School of Medicine, Tokyo, Japan.
Cancer Res. 1992 Feb 1;52(3):696-700.
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.
α-二氟甲基鸟氨酸(DFMO)治疗已被证明可在许多实验性肿瘤模型中改变致癌作用,包括乳腺癌、膀胱癌和结肠癌。本研究旨在确定DFMO治疗是否能抑制大鼠化学诱导的结肠癌的肿瘤生长。还评估了DFMO与丝裂霉素C(MMC)联合使用的有效性。42只Sprague-Dawley大鼠皮下注射二甲基肼(20mg/kg),每周一次,共20周以诱导结肠癌。然后进行双重对比钡灌肠,并检测结肠肿瘤。将动物分为四组,进行以下治疗:不治疗;单独使用DFMO;单独使用MMC;DFMO加MMC联合使用。治疗5周后,重复进行钡灌肠。为评估治疗效果,采用肿瘤倍增时间。对照组的平均肿瘤倍增时间为20.7±9.1天(标准差)。当治疗组的肿瘤倍增时间超过38.9天时,判定为“有反应”,该时间是根据对照组的平均值+2个标准差计算得出的。DFMO组、MMC组和DFMO加MMC组的反应率分别为40.0%、10.0%和82.3%。DFMO比MMC更有效地抑制肿瘤生长,并且DFMO与MMC联合使用可协同减少肿瘤生长。双重对比钡灌肠有助于观察肿瘤的连续生长,可能适用于评估大鼠实验性结肠癌的新治疗方法。