Pasricha P J, Bedi A, O'Connor K, Rashid A, Akhtar A J, Zahurak M L, Piantadosi S, Hamilton S R, Giardiello F M
Department of Medicine, Johns Hopkins University School of Medicine and Hospital, Baltimore, Maryland, USA.
Gastroenterology. 1995 Sep;109(3):994-8. doi: 10.1016/0016-5085(95)90411-5.
BACKGROUND & AIMS: The mechanism by which sulindac causes regression of adenomas in patients with familial adenomatous polyposis (FAP) is unclear. Conflicting data on the drug's effects on colorectal epithelial proliferation have been reported. An alternative mechanism, and one not previously studied, is via induction of colorectal epithelial cell apoptosis (programmed cell death). This hypothesis was tested by studying the effects of sulindac on colorectal epithelial proliferation and apoptosis in patients with FAP.
Cell proliferation was studied via immunohistochemistry for cell nuclear antigen in a group of 22 patients randomized to either sulindac (150 mg twice a day) or placebo in a previously published trial. The rectal epithelium from 7 additional patients with FAP treated with sulindac was examined by flow cytometry to assess changes in cell-cycle distribution and apoptosis.
Although sulindac caused a significant decrease in polyp size and number, there was no significant change in cytokinetic variables or cell cycle distribution 3 months after treatment. However, the subdiploid apoptotic fraction was increased significantly 3 months after treatment with sulindac (31.3% +/- 4.8% compared with 10% +/- 4.3% at baseline; P = 0.01).
Our findings suggest that sulindac does not affect colorectal epithelial proliferation and that its effects in patients with FAP may instead result from induction of apoptosis.
舒林酸使家族性腺瘤性息肉病（FAP）患者腺瘤消退的机制尚不清楚。关于该药物对结直肠上皮增殖作用的数据相互矛盾。一种尚未被研究过的替代机制是通过诱导结直肠上皮细胞凋亡（程序性细胞死亡）。通过研究舒林酸对FAP患者结直肠上皮增殖和凋亡的影响来验证这一假设。
在一项先前发表的试验中，对一组22例随机分为舒林酸组（150mg，每日2次）或安慰剂组的患者，通过免疫组化检测细胞核抗原研究细胞增殖。另外，对7例接受舒林酸治疗的FAP患者的直肠上皮进行流式细胞术检测，以评估细胞周期分布和凋亡的变化。
尽管舒林酸使息肉大小和数量显著减少，但治疗3个月后细胞动力学变量或细胞周期分布没有显著变化。然而，舒林酸治疗3个月后亚二倍体凋亡分数显著增加（31.3%±4.8%，而基线时为10%±4.3%；P=0.01）。
我们的研究结果表明，舒林酸不影响结直肠上皮增殖，其在FAP患者中的作用可能是通过诱导凋亡产生的。
