Department of Biochemistry and Microbiology, Joan Edwards School of Medicine, Marshall University, Huntington, West Virginia, United States of America.
PLoS One. 2013 Jul 16;8(7):e69760. doi: 10.1371/journal.pone.0069760. Print 2013.
Colorectal cancer is the third leading cause of cancer-related death in the western world. In vitro and in vivo experiments showed that omega-3 polyunsaturated fatty acids (n-3 PUFAs) can attenuate the proliferation of cancer cells, including colon cancer, and increase the efficacy of various anticancer drugs. However, these studies address the effects of n-3 PUFAs on the bulk of the tumor cells and not on the undifferentiated colon cancer stem-like cells (CSLCs) that are responsible for tumor formation and maintenance. CSLCs have also been linked to the acquisition of chemotherapy resistance and to tumor relapse. Colon CSLCs have been immunophenotyped using several antibodies against cellular markers including CD133, CD44, EpCAM, and ALDH. Anti-CD133 has been used to isolate a population of colon cancer cells that retains stem cells properties (CSLCs) from both established cell lines and primary cell cultures. We demonstrated that the n-3 PUFA, eicosapentaenoic acid (EPA), was actively incorporated into the membrane lipids of COLO 320 DM cells. 25 uM EPA decreased the cell number of the overall population of cancer cells, but not of the CD133 (+) CSLCs. Also, we observed that EPA induced down-regulation of CD133 expression and up-regulation of colonic epithelium differentiation markers, Cytokeratin 20 (CK20) and Mucin 2 (MUC2). Finally, we demonstrated that EPA increased the sensitivity of COLO 320 DM cells (total population) to both standard-of-care chemotherapies (5-Fluorouracil and oxaliplatin), whereas EPA increased the sensitivity of the CD133 (+) CSLCs to only 5-Fluorouracil.
结直肠癌是西方世界癌症相关死亡的第三大主要原因。体外和体内实验表明，ω-3 多不饱和脂肪酸（n-3PUFAs）可以抑制癌细胞的增殖，包括结肠癌，并提高各种抗癌药物的疗效。然而，这些研究仅关注 n-3PUFAs 对肿瘤细胞群体的影响，而不关注负责肿瘤形成和维持的未分化结肠癌类干细胞（CSLCs）。CSLCs 还与获得化疗耐药性和肿瘤复发有关。使用针对细胞标志物（包括 CD133、CD44、EpCAM 和 ALDH）的几种抗体对结肠 CSLCs 进行了免疫表型分析。抗 CD133 已被用于从已建立的细胞系和原代细胞培养物中分离保留干细胞特性（CSLCs）的结肠癌细胞群体。我们证明，n-3PUFA，二十碳五烯酸（EPA），被主动掺入 COLO 320 DM 细胞的膜脂质中。25 μM EPA 减少了癌细胞总体群的细胞数量，但对 CD133（+）CSLCs 没有影响。此外，我们观察到 EPA 诱导 CD133 表达下调和结肠上皮分化标志物细胞角蛋白 20（CK20）和粘蛋白 2（MUC2）上调。最后，我们证明 EPA 增加了 COLO 320 DM 细胞（总体群）对标准护理化疗药物（5-氟尿嘧啶和奥沙利铂）的敏感性，而 EPA 仅增加了 CD133（+）CSLCs 对 5-氟尿嘧啶的敏感性。
