ARACHIDONIC-ACID METABOLISM IN BENIGN AND MALIGNANT PROSTATIC TISSUE IN-VITRO - EFFECTS OF FATTY-ACIDS AND CYCLOOXYGENASE INHIBITORS
ARACHIDONIC-ACID METABOLISM IN BENIGN AND MALIGNANT PROSTATIC TISSUE IN-VITRO - EFFECTS OF FATTY-ACIDS AND CYCLOOXYGENASE INHIBITORS
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DOI：
10.1002/ijc.2910570208
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发表时间：
1994-04-15
影响因子：
6.4
通讯作者：
MOFFAT, LEF
中科院分区：
文献类型：
--
作者：
CHAUDRY, AA;WAHLE, KWJ;MOFFAT, LEF
此前已证明，良性或恶性前列腺疾病患者前列腺组织中的脂肪酸（FA）浓度存在显着差异。特别是，恶性前列腺组织 (PCa) 磷脂 (PL) 中的花生四烯酸 (AA, C20:4n-6) 和二十二碳五烯酸 (DPA, C22:5n-6) 浓度显着降低。有人提出，PCa 中 AA 浓度的降低可能是由于其通过环氧合酶 (CO) 和/或脂氧合酶 (LO) 途径产生类二十烷酸（如前列腺素 (PG) 和/或白三烯 (LT)）的代谢增加，而不是原位去饱和酶活性受损。使用 [H-3]AA 测定良性前列腺组织 (BPH) 和 PCa 中类二十烷酸的产生。两种组织中唯一大量产生的类二十烷酸是 PGE(2)，PCa 将放射性标记的 AA 转化为 PGE(2)，在存在油酸 (OA, C18:In-9)、(DHA, C22:n-3)、二高-γ-亚麻酸 (DGLA, C20:3n-6)、 分别是二十碳四烯酸（ETYA）和酮洛芬（KPN）。与 DHA、EPA、ETYA 和 KPN 相比，OA 是 PCa 产生 PGE(2) 的最有效抑制剂，而 DGLA 的效果最差。 PCa 标记的 AA 形成的二酰基甘油 (DAG) 比 BPH 多约 4 倍。如此高水平的 DAG 可能是通过激活蛋白激酶 C 促进肿瘤发生的一种手段，如佛波酯（可被视为 DAG 类似物）所发现的那样。 (C) 1994 年 Wiley-Liss 公司
Concentration of fatty acids (FA) in prostatic tissue of patients with either benign or malignant prostatic disease have previously been shown to be significantly different. In particular, there was a significant reduction in arachidonic acid (AA, C20:4n-6) and docosapentaenoic acid (DPA, C22:5n-6) concentrations in malignant prostatic tissue (PCa) phospholipids (PL). It was suggested that the decreased AA concentration in PCa may be due to its increased metabolism via the cyclooxygenase (CO) and/or lipoxygenase (LO) pathways to produce eicosanoids such as prostaglandins (PGs) and/or leucotrienes (LTs) rather than an impairment in desaturase activity in situ. The eicosanoid production in benign prostatic tissue (BPH) and PCa was determined using [H-3]AA. The only eicosanoid produced in significant amounts by either tissue was PGE(2) and PCa converted radiolabelled AA to PGE(2) production from [H-3]AA by PCa was investigated in the presence of oleic acid (OA, C18:In-9), (DHA, C22:n-3), dihomo-gamma-linolenic acid (DGLA, C20:3n-6), eicosatetraynoic acid (ETYA) and ketoprofen (KPN) respectively. OA was found to be the most effective inhibitor of PGE(2) production by PCa compared with DHA, EPA, ETYA and KPN, while DGLA was the least effective. Diacylglycerol (DAG) formation from labelled AA by PCa was about 4-fold greater than in BPH. Such high levels of DAG may be a means of promoting tumorigenesis through activation of protein kinase C as found with phorbol esters which can be regarded as DAG analogues. (C) 1994 Wiley-Liss, Inc.