EFFECT OF POLYUNSATURATED FATTY-ACIDS ON THE GROWTH OF MURINE COLON ADENOCARCINOMAS IN-VITRO AND IN-VIVO
EFFECT OF POLYUNSATURATED FATTY-ACIDS ON THE GROWTH OF MURINE COLON ADENOCARCINOMAS IN-VITRO AND IN-VIVO
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DOI：
10.1038/bjc.1994.241
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发表时间：
1994-07-01
影响因子：
8.8
通讯作者：
TISDALE, MJ
中科院分区：
文献类型：
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作者：
HUSSEY, HJ;TISDALE, MJ
多不饱和脂肪酸 (PUFA)、亚油酸 (LA) 和花生四烯酸 (AA) 对两种小鼠结肠腺癌细胞系（MAC26 和 MAC13）生长的影响已在体外和体内测定。当培养基中的血清浓度变得生长受限时，低浓度（18-33μM）的两种PUFA对两种细胞系都具有生长刺激作用，而较高浓度则抑制生长。两种细胞系中 AA 以及 MAC13 中 LA 的生长刺激均被环加氧酶和脂氧合酶抑制剂吲哚美辛以及脂氧合酶抑制剂 BWA4C 有效抑制，且呈剂量依赖性。 BWA4C 发挥了最有效的抑制作用，表明两种 PUFA 通过脂氧合酶途径进行代谢以刺激生长。使用MAC26肿瘤的体内研究表明，当口服LA浓度高于0.4 g kg(-1) day(-1)时，可显着刺激肿瘤生长。较高的浓度不会导致肿瘤生长速率进一步增加。这表明 LA 刺激生长存在一个阈值剂量，与饮食中的 LA 一起达到总热量摄入的 3.8%。 LA引起的肿瘤体积增加是由于潜在倍增时间从41小时缩短至28小时，并被吲哚美辛（5 mg kg(-1)）有效逆转。这些结果表明PUFA可能在肿瘤生长中发挥重要作用，并可能为化疗药物的开发提供潜在靶点。
The effect of the polyunsaturated fatty acids (PUFAs) linoleic acid (LA) and arachidonic acid (AA) on the growth of two murine colon adenocarcinoma cell lines (MAC26 and MAC13) has been determined both in vitro and in vivo. When the serum concentration in the medium became growth limiting, low concentrations (18-33 mu M) of both PUFAs were growth stimulatory to both cell lines, while higher concentrations were growth inhibitory. Growth stimulation by AA in both cell lines, and by LA in MAC13, was effectively inhibited by both the cyclo-oxygenase and lipoxygenase inhibitor indomethacin, and the lipoxygenase inhibitor BWA4C in a dose-dependent manner. The most effective inhibition was exerted by BWA4C, suggesting metabolism of both PUFAs through the lipoxygenase pathway for growth stimulation. In vivo studies using the MAC26 tumour showed a significant stimulation of tumour growth when LA was administered orally at concentrations higher than 0.4 g kg(-1) day(-1). Higher concentrations did not produce a further increase in tumour growth rate. This suggests that there is a threshold dose for growth stimulation by LA which, together with that in the diet, amounted to 3.8% of the total caloric intake. The increase in tumour volume induced by LA arose from a reduction in the potential doubling time from 41 to 28 h and was effectively reversed by indomethacin (5 mg kg(-1)). These results suggest that PUFAs may play an important role in tumour growth and may offer a potential target for the development of chemotherapeutic agents.