Yue Chung-Tai, Liu Yu-Li
Department of Pathology, National Cheng Kung University, Taiwan, R.O.C.
Cell Biochem Funct. 2005 Mar-Apr;23(2):109-14. doi: 10.1002/cbf.1193.
Fluoxetine (Prozac) is a serotonin reuptake inhibitor. It increases extracellular levels of serotonin and is used in relieving the depressive symptoms of cancer patients. It has been reported that the drug may enhance the growth of certain cancer cells. This study investigates whether fluoxetine enhances the growth of a human colon cancer cell line (COLO320 DM) and if it affects the extracellular levels of serotonin or its metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA) and other monoamines and metabolites at two cell densities. The extracellular levels of serotonin, 5-HIAA and other monoamines and metabolites were measured simultaneously by high performance liquid chromatography from cell-culture media after incubation of cells both with and without fluoxetine for 3 days. The viability of COLO320 DM cells was evaluated using 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). At low cell densities (1.25x10(5) cells ml-1), fluoxetine at 1-10 microM significantly increased the extracellular levels of serotonin (p<0.005), 5-HIAA (p<0.005), and 3-methoxy-4-hydroxyphenylglycol (MHPG; p<0.001) as compared to the controls. Fluoxetine at 10-100 microM significantly inhibited the growth of COLO320 DM (p<0.005). At high cell densities (2x10(6) cells ml-1), fluoxetine at 1-10 microM significantly increased the extracellular levels of MHPG (p<0.01), and at 10 microM it significantly increased the extracellular levels of 5-HIAA (p<0.05). Fluoxetine at 100 microM significantly inhibited the growth of the cells (p<0.0001). These results suggest that fluoxetine at 1 microM of effective concentration may increase the extracellular levels MHPG, in addition to serotonin and 5-HIAA levels, yet not inhibit the growth of COLO320 DM.
氟西汀（百忧解）是一种血清素再摄取抑制剂。它能提高细胞外血清素水平，用于缓解癌症患者的抑郁症状。据报道，该药物可能会促进某些癌细胞的生长。本研究调查了氟西汀是否会促进人结肠癌细胞系（COLO320 DM）的生长，以及它在两种细胞密度下是否会影响血清素或其代谢产物5-羟吲哚-3-乙酸（5-HIAA）以及其他单胺和代谢产物的细胞外水平。在细胞分别与氟西汀一起孵育3天和不与氟西汀孵育的情况下，通过高效液相色谱法同时测量细胞培养基中血清素、5-HIAA以及其他单胺和代谢产物的细胞外水平。使用3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四氮唑（MTT）评估COLO320 DM细胞的活力。在低细胞密度（1.25×10⁵个细胞/毫升）下，与对照组相比，1 - 10微摩尔的氟西汀显著提高了血清素（p<0.005）、5-HIAA（p<0.005）和3-甲氧基-4-羟基苯乙二醇（MHPG；p<0.001）的细胞外水平。10 - 100微摩尔的氟西汀显著抑制了COLO320 DM的生长（p<0.005）。在高细胞密度（2×10⁶个细胞/毫升）下，1 - 10微摩尔的氟西汀显著提高了MHPG的细胞外水平（p<0.01），10微摩尔时显著提高了5-HIAA的细胞外水平（p<0.05）。100微摩尔的氟西汀显著抑制了细胞的生长（p<0.0001）。这些结果表明，有效浓度为1微摩尔的氟西汀除了能提高血清素和5-HIAA水平外，还可能提高MHPG的细胞外水平，但不会抑制COLO320 DM的生长。
