Hixson L J, Alberts D S, Krutzsch M, Einsphar J, Brendel K, Gross P H, Paranka N S, Baier M, Emerson S, Pamukcu R
Department of Medicine, University of Arizona, Tucson 85724.
Cancer Epidemiol Biomarkers Prev. 1994 Jul-Aug;3(5):433-8.
Several lines of evidence suggest that nonsteroidal antiinflammatory drugs may be effective in preventing colorectal cancer. These include animal experiments, case-control studies, and clinical experience with sulindac in promoting the regression of adenomatous colon polyps in adenomatous polyposis coli. We determined the antiproliferative activity of various nonsteroidal antiinflammatory drugs, including two sulindac derivatives, against human colon cancer cells in vitro. Ht-29, SW480, and DLD-1 cells were continuously incubated with serial drug dilutions for 6 days prior to fixation. Cell number was determined using the sulforhodamine B assay, and drug concentrations which inhibited cell growth by 50% were estimated for each agent by interpolation. All drugs exhibited antiproliferative activity against Ht-29 and DLD-1 cells, and most inhibited SW480 cells. For Ht-29 cells, the 50% inhibitory concentration varied from 55 microM for diclofenac to 2100 microM for 5-aminosalicylic acid, with three drug groups of high, intermediate, and low potency evident. Inhibition of cell growth by sulindac sulfide was reversible following drug removal. Nonsteroidal antiinflammatory drugs exert an antiproliferative effect against human colon cancer cells with a wide range of potencies. A cytostatic response was demonstrated with sulindac sulfide. These data further support the potential role of these agents for chemoprevention of colorectal neoplasia.
多项证据表明，非甾体抗炎药可能对预防结直肠癌有效。这些证据包括动物实验、病例对照研究，以及舒林酸促进家族性腺瘤性息肉病患者腺瘤性结肠息肉消退的临床经验。我们测定了包括两种舒林酸衍生物在内的多种非甾体抗炎药对人结肠癌细胞的体外抗增殖活性。在固定前，将Ht-29、SW480和DLD-1细胞与系列药物稀释液连续孵育6天。使用磺酰罗丹明B法测定细胞数量，并通过插值法估算每种药物抑制细胞生长50%时的浓度。所有药物均对Ht-29和DLD-1细胞表现出抗增殖活性，且大多数药物能抑制SW480细胞。对于Ht-29细胞，50%抑制浓度范围从双氯芬酸的55微摩尔到5-氨基水杨酸的2100微摩尔，明显分为高、中、低效能三个药物组。去除药物后，舒林酸硫化物对细胞生长的抑制作用是可逆的。非甾体抗炎药对人结肠癌细胞具有广泛的抗增殖作用，舒林酸硫化物表现出细胞生长抑制反应。这些数据进一步支持了这些药物在结直肠癌化学预防中的潜在作用。
