Decreased 13-S-hydroxyoctadecadienoic acid levels and 15-lipoxygenase-1 expression in human colon cancers
Decreased 13-S-hydroxyoctadecadienoic acid levels and 15-lipoxygenase-1 expression in human colon cancers
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DOI：
10.1093/carcin/20.10.1985
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发表时间：
1999-10-01
期刊：
影响因子：
4.7
通讯作者：
Brenner, DE
中科院分区：
文献类型：
--
作者：
Shureiqi, I;Wojno, KJ;Brenner, DE
13-S-羟基十八烯酸(13-S-HODE)是亚油酸15-脂氧合酶(15-LOX)代谢的产物，可增强细胞对某些生长因子的促有丝分裂反应。其他观察结果也质疑13-S-HODE是否具有致癌作用。本研究对15-LOX-1在结肠癌中高表达导致细胞内13-S-HODE增加的假说进行了评价，并用Western blotts、ELISA法和免疫组织化学方法对18例结肠癌和配对的正常结肠黏膜进行了15-LOX-1和13-S-HODE的定量。此外，通过免疫印迹法检测了15-LOX-1在三个转化的结肠细胞系和一个人脐静脉内皮细胞系中的表达。接下来，我们研究了13-S对转化的结肠癌细胞系的细胞增殖、细胞周期分布和细胞凋亡的影响。流式细胞仪检测细胞周期分布，相差显微镜、电子显微镜、流式细胞仪和DNA片段法检测细胞凋亡率。肿瘤组织中15-LOX-1免疫组织化学染色积分降低(P<0.0001)，3株转化的结肠细胞系均无15-LOX-1表达。用ELISA法和免疫组化法检测肿瘤组织中13-S-HODE的水平也低于正常对照组(中位数为3.33倍，P=0.02，P<0.0001)。在体外，13-S-HODE抑制RKO细胞的增殖，诱导细胞周期停滞和凋亡，13-S-HODE对HT-29细胞也有类似的作用。我们的观察表明：(I)人结肠癌与15-LOX-1表达下调和13-S-HODE细胞内水平降低有关；(Ii)13-S-HODE能抑制转化的结肠上皮细胞增殖并诱导其凋亡。
13-S-Hydroxyoctadecadienoic acid (13-S-HODE), the product of 15-lipoxygenase (15-LOX) metabolism of linoleic acid, enhances cellular mitogenic responses to certain growth factors. Other observations have questioned whether 13-S-HODE has tumorigenic effects. Our study evaluated the hypothesis that 15-LOX-1 is overexpressed in colon cancers resulting in an increase in intracellular 13-S-HODE, 15-LOX-1 and 13-S-HODE were quantified using western blots, ELISA and immunohistochemistry in 18 human colon cancers with paired normal colonic mucosa. Additionally, 15-LOX-1 expression was measured by western blots in three transformed colonic cell lines and in a human umbilical vein endothelial cell line. Next, we evaluated 13-S-HODE effects on cellular proliferation, cell cycle distribution and apoptosis in a transformed colonic cell line (RKO). Cell cycle distributions were measured by flow cytometry and apoptosis was assessed by phase contrast microscopy, electron microscopy, flow cytometry and DNA fragmentation assay. 15-LOX-1 immunohistochemistry staining scores were reduced in tumor tissues (P less than or equal to 0.0001) and 15-LOX-1 expression was absent in three transformed colonic cell lines. 13-S-HODE levels were also reduced in tumors tissues compared with normal controls by ELISA (median 3.3-fold, P = 0.02) and by immunohistochemistry (P less than or equal to 0.0001). In vitro 13-S-HODE inhibited RKO cell proliferation and induced cell cycle arrest and apoptosis, 13-S-HODE produced similar effects in HT-29 cells. Our observations indicate that: (i) human colon cancers are associated with a down-regulation in 15-LOX-1 expression and a reduction in 13-S-HODE intracellular levels; (ii) 13-S-HODE can suppress cell proliferation and induce apoptosis in transformed colonic epithelial cells.