Anti-cancer effects of morphine through inhibition of tumour necrosis factor-alpha release and mRNA expression
Anti-cancer effects of morphine through inhibition of tumour necrosis factor-alpha release and mRNA expression
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DOI：
10.1093/carcin/17.11.2337
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发表时间：
1996-11-01
期刊：
影响因子：
4.7
通讯作者：
Fujiki, H
中科院分区：
文献类型：
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作者：
Sueoka, N;Sueoka, E;Fujiki, H
吗啡主要用于缓解晚期癌症患者的疼痛，我们发现吗啡对多种人癌细胞系的生长具有抑制作用，IC_（50）为2.7 - 8.8mM，对BALB/3T_3细胞的IC_（50）为1.5mM，虽然IC_（50）值相对较高，但我们决定研究吗啡抗肿瘤作用的机制。吗啡抑制由teleocidin诱导的蛋白激酶C的活化，teleocidin是12-O-十四酰基佛波醇-13-乙酸酯（TPA）型肿瘤促进剂之一（IC 50，1 mM）。基于我们之前的证据肿瘤坏死因子-α TNF-α在3-甲基胆蒽诱导的BALB/3 T3细胞上作为内源性肿瘤促进剂，我们发现吗啡剂量依赖性地抑制KATO III细胞TNF-α的释放（IC 50，5.6 mM），也来自BALB/3 T3细胞（IC 50，1.3mM），此外，吗啡可抑制BALB/3 T3细胞TNF-α mRNA的表达（IC_（50）为1.6mM），但对TNF-α mRNA的表达无明显影响。不表达早期反应基因，吗啡可以通过抑制肿瘤生长和减少组织中内源性肿瘤促进因子TNF-α的量来改善癌症患者的状况。
Morphine is mainly used to relieve pain in the terminal stage of cancer patients, We found that morphine has inhibitory effects on growth of various human cancer cell lines, with IC50 from 2.7 to 8.8 mM, and BALB/3T3 cells, with IC50 of 1.5 mM. Although the IC50 values were relatively high, we decided to study the mechanisms of anti-carcinogenic effects of morphine. Morphine inhibited activation of protein kinase C induced by teleocidin, one of the 12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumour promoters (IC50, 1 mM). Based on our previous evidence that tumour necrosis factor-alpha (TNF-alpha) acts as an endogenous tumour promoter on BALB/3T3 cells initiated with 3-methylcholanthrene, we found that morphine dose-dependently inhibited TnF-alpha release from KATO III cells (IC50, 5.6 mM) and also from BALB/3T3 cells (IC50, 1.3 mM) induced by okadaic acid, one of the non-TPA type tumour promoters, Moreover, morphine inhibited expression of TNF-alpha mRNA in BALB/3T3 cells (IC50, 1.6 mM), but. not expression of early response genes, Morphine may improve condition of cancer patients by suppression of tumour growth and reduction of amounts of an endogenous tumor promoter, TNF-alpha, in tissues, The high dosage of morphine required to induce anti-carcinogenic effects is also discussed.