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Cyclooxygenase-independent chemoprevention with an aspirin derivative in a rat model of colonic adenocarcinoma

机译：阿司匹林衍生物不依赖环加氧酶的化学预防在结肠腺癌大鼠模型中的作用

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Aspirin decreases the risk of colorectal cancer, reportedly through suppression of cyclooxygenase (COX) activity. Using a rat model of colonic adenocarcinoma, we compared the chemopreventative effects of aspirin versus a nitric oxide-releasing derivative (NCX-4016) which does not inhibit COX. Beginning six weeks after intracolonic administration of trinitrobenzene sulfonic acid, the rats were given azoxymethane weekly (15 mg/kg i.p.) for 4 weeks. Over the same 4-week period, the rats were treated daily with vehicle, aspirin (10 mg/kg) or NCX-4016 (equimolar dose). Six weeks later, the number of aberrant crypt foci (an early preneoplastic lesion) were blindly counted by light microscopy. Effects of aspirin vs. NCX-4016 on COX-1 and COX-2 activity were compared, as was their analgesic activity Rats receiving vehicle developed a mean of 856 +/- 260 aberrant crypt foci in the colon. Aspirin reduced the number of aberrant crypt foci by 64%, while NCX-4016 produced an 85% reduction. Aspirin, but not NCX-4016, markedly suppressed systemic COX-1 and COX-2 activity, and colonic prostaglandin synthesis. Despite not inhibiting COX, NCX-4016 exhibited comparable analgesic activity to aspirin. These results demonstrate that NCX-4016, a nitric oxide-releasing aspirin derivative, exhibited superior chemopreventative effects to aspirin in this model of colon cancer. This effect occurred independent of inhibition of COX-1 or COX-2. (C) 1998 Elsevier Science Inc. [References: 27]
机译：据报道，阿司匹林可通过抑制环氧合酶（COX）的活性来降低结直肠癌的风险。使用大鼠结肠腺癌模型，我们比较了阿司匹林与不抑制COX的一氧化氮释放衍生物（NCX-4016）的化学预防作用。在结肠内施用三硝基苯磺酸后六周开始，每周给大鼠施用甲氧甲烷（15 mg / kg腹腔注射），持续4周。在相同的4周时间内，每天用赋形剂，阿司匹林（10 mg / kg）或NCX-4016（等剂量）治疗大鼠。六周后，通过光学显微镜盲目计数异常的隐窝灶数目（早期肿瘤前病变）。比较了阿司匹林与NCX-4016对COX-1和COX-2活性的影响，以及它们的镇痛活性，比较了接受媒介物的大鼠在结肠中平均产生了856 +/- 260个异常隐窝灶。阿司匹林使异常隐窝病灶数量减少了64％，而NCX-4016减少了85％。阿司匹林（而非NCX-4016）显着抑制全身性COX-1和COX-2活性以及结肠前列腺素合成。尽管不抑制COX，NCX-4016的镇痛活性却与阿司匹林相当。这些结果表明，在该结肠癌模型中，释放一氧化氮的阿司匹林衍生物NCX-4016表现出优于阿司匹林的化学预防作用。产生这种效应与抑制COX-1或COX-2无关。 （C）1998 Elsevier Science Inc. [参考：27]

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