Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells.
Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells.
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发表时间：
1998-01
期刊：
影响因子：
11.2
通讯作者：
H. Sheng;J. Shao;J. Morrow;R. Beauchamp;R. Dubois
中科院分区：
文献类型：
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作者：
H. Sheng;J. Shao;J. Morrow;R. Beauchamp;R. Dubois
以前，我们已经表明，前列腺素内过氧化物合酶-2 [也称为环氧合酶（考克斯）2]的强制表达导致肠上皮细胞程序性细胞死亡的抑制。最近，我们已经证明，在表达考克斯-2（HCA-7）的肿瘤中，用高度选择性的考克斯-2抑制剂治疗可以抑制人结肠癌异种移植物的生长，但在缺乏考克斯-2表达的肿瘤（HCT-116）中则不能。为了探索这些作用的生化机制，我们评估了考克斯-2衍生的类花生酸产物对人结肠癌细胞程序性细胞死亡的作用。在这里，我们报告说，前列腺素E2治疗的人结肠癌细胞导致增加的克隆形成HCA-7，但不是HCT-116细胞。用高度选择性的考克斯-2抑制剂（SC-58125）处理可减少单层培养物中的集落形成，而用PGE 2处理可逆转这种生长抑制。此外，PGE 2抑制由SC-58125引起的程序性细胞死亡并诱导Bcl-2表达，但不影响人结肠癌（HCA-7）细胞中Bcl-x或Bax的表达。因此，减少由PGE 2引起的细胞死亡将增强肠上皮细胞的致瘤潜力。因此，这些结果可能有助于解释考克斯抑制剂预防人类结直肠癌的机制。
Previously, we have shown that forced expression of prostaglandin endoperoxide synthase-2 [also called cyclooxygenase (COX) 2] leads to inhibition of programmed cell death in intestinal epithelial cells. More recently, we have demonstrated that growth of human colonic cancer xenografts is inhibited by treatment with a highly selective COX-2 inhibitor in tumors that express COX-2 (HCA-7) but not in those that lack COX-2 expression (HCT-116). To explore the biochemical mechanisms involved in these effects, we have evaluated the role of COX-2-derived eicosanoid products on programmed cell death in human colon cancer cells. Here we report that PGE2 treatment of human colon cancer cells leads to increased clonogenicity of HCA-7, but not HCT-116 cells. Treatment with a highly selective COX-2 inhibitor (SC-58125) decreases colony formation in monolayer culture and this growth inhibition was reversed by treatment with PGE2. Additionally, PGE2 inhibits programmed cell death caused by SC-58125 and induces Bcl-2 expression, but did not affect Bcl-x or Bax expression in human colon cancer (HCA-7) cells. Therefore, decreased cell death caused by PGE2 would enhance the tumorigenic potential of intestinal epithelial cells. Thus, these results may help to explain a component of the mechanism by which COX inhibitors prevent colorectal cancer in humans.