Pereira M A, Barnes L H, Steele V E, Kelloff G V, Lubet R A
Environmental Health Research and Testing Inc., Lexington, KY 40503, USA.
Carcinogenesis. 1996 Feb;17(2):373-6. doi: 10.1093/carcin/17.2.373.
Piroxicam has been shown to prevent azoxymethane (AOM)-induced aberrant crypt foci and colon cancer in rats. In this communication we evaluate whether piroxicam can also cause regression of precancerous lesions identified as aberrant crypt foci, thus preventing the occurrence of cancer. Male Fischer-344 rats were administered 0.125 g/kg piroxicam in their diet starting either 1 week prior to or 12 weeks after a single subcutaneous injection of AOM (30 mg/kg body wt). The yield of aberrant crypt foci and of colon adenomas and adenocarcinomas was determined at 5, 12, 27 and 37 weeks after administering the AOM respectively. When piroxicam was administered starting 1 week prior to AOM the yield of aberrant crypt foci at the three initial time points was reduced. When the administration of piroxicam was delayed until 12 weeks after AOM the yield of aberrant crypt foci was reduced from 53.8 +/- 8.1 foci/colon at 12 weeks to 11.1 +/- 2.0 at 27 weeks. At 37 weeks after administering AOM the yield of colon tumors was 0.59 +/- 0.11 tumors/animal, while in rats administered piroxicam beginning either 1 week prior to or 12 weeks after AOM the yield was similarly reduced to 0.14 +/- 0.07 and 0.17 +/- 0.07 tumors/animal respectively. Thus piroxicam was demonstrated not only to prevent, but also to cause regression of aberrant crypt foci, both of which were associated with the prevention of colon tumors.
吡罗昔康已被证明可预防大鼠中由氧化偶氮甲烷(AOM)诱导的异常隐窝灶和结肠癌。在本通讯中,我们评估吡罗昔康是否也能使被鉴定为异常隐窝灶的癌前病变消退,从而预防癌症的发生。雄性Fischer-344大鼠在单次皮下注射AOM(30mg/kg体重)前1周或后12周开始,在其饮食中给予0.125g/kg吡罗昔康。分别在给予AOM后的5、12、27和37周测定异常隐窝灶以及结肠腺瘤和腺癌的发生率。当在AOM前1周开始给予吡罗昔康时,最初三个时间点的异常隐窝灶发生率降低。当吡罗昔康的给药延迟至AOM后12周时,异常隐窝灶的发生率从12周时的53.8±8.1个/结肠降至27周时的11.1±2.0个。在给予AOM后37周,结肠肿瘤的发生率为0.59±0.11个/动物,而在AOM前1周或后12周开始给予吡罗昔康的大鼠中,发生率同样分别降至0.14±0.07和0.17±0.07个/动物。因此,吡罗昔康不仅被证明可预防,还能使异常隐窝灶消退,这两者均与结肠肿瘤的预防相关。