Jordan Angela, Stein Jürgen
2nd Dept. of Medicine, Johann Wolfgang Goethe University, Theodor Stern Kai 7, 60590, Frankfurt, Germany.
Eur J Nutr. 2003 Dec;42(6):324-31. doi: 10.1007/s00394-003-0427-1.
In this study we examined the effects of a fish oil-based lipid emulsion (FO) rich in omega-3 fatty acids, which is used in humans as a component of parenteral nutrition, on the growth of the colon cancer cell line Caco-2.
The aim of the present study was to investigate whether the FO influences growth and chemosensitivity of the colon cancer cell line Caco-2. FO was tested alone and in combination with the anticancer drug 5-fluorouracil (5-FU).
Cell numbers were determined with crystal violet staining, cell cycle distribution was assessed using a flow cytometer and apoptosis was visualized by staining nuclei with diamino-phenylindole hydrochloride.
FO inhibited growth of Caco-2 cells in a time and dose dependent manner. FO treatment evoked apoptosis as confirmed by cell morphology. Cell cycle analysis identified an accumulation of cells in the G(2)/M phase after incubation with FO. The combined treatment of the cells with FO and 5-FU resulted in a significant enhancement of the growth inhibition seen after exposure to either substance alone. Treatment of the cells with 5-FU specifically blocked the cell cycle in the S phase. The combined treatment of 5-FU with FO showed a further increase in the accumulation of cells in the S phase.
In conclusion, FO has a potent antiproliferative effect on Caco-2 cells, at least in part, due to a decrease in the progression of the cell cycle and the induction of apoptosis. The combination of FO with 5-FU results in an additive growth inhibitory effect.
在本研究中，我们检测了富含ω-3脂肪酸的鱼油基脂质乳剂（FO）对结肠癌细胞系Caco-2生长的影响，该脂质乳剂在人体中用作肠外营养的一种成分。
本研究的目的是调查FO是否影响结肠癌细胞系Caco-2的生长和化学敏感性。单独对FO进行了测试，并将其与抗癌药物5-氟尿嘧啶（5-FU）联合进行了测试。
用结晶紫染色法测定细胞数量，使用流式细胞仪评估细胞周期分布，并用盐酸二氨基苯基吲哚对细胞核进行染色来观察细胞凋亡情况。
FO以时间和剂量依赖性方式抑制Caco-2细胞的生长。细胞形态学证实FO处理可诱发细胞凋亡。细胞周期分析表明，与FO孵育后，细胞在G(2)/M期积累。FO与5-FU联合处理细胞导致单独暴露于任何一种物质后所观察到的生长抑制作用显著增强。用5-FU处理细胞可特异性地阻断S期的细胞周期。5-FU与FO联合处理显示S期细胞积累进一步增加。
总之，FO对Caco-2细胞具有强大的抗增殖作用，至少部分原因是细胞周期进程的减慢和细胞凋亡的诱导。FO与5-FU联合使用可产生相加的生长抑制作用。
