乙酰水杨酸（ASA）可保护人肾上腺癌细胞的前列腺素 - cAMP 系统免受辐射诱导的改变。

Acetylsalicylic acid (ASA) protects the prostaglandin-cAMP-system of human hypernephroma cells against irradiation-induced alterations.

作者信息

Li S R, Yang Q, Wandl E, Pirker W, Virgolini I

机构信息

Department of Nuclear Medicine, University of Vienna, Austria.

出版信息

Br J Cancer. 1993 Oct;68(4):695-701. doi: 10.1038/bjc.1993.412.

DOI:10.1038/bjc.1993.412

PMID:7691143

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1968618/

Abstract

There is abundant evidence that inhibitors of prostaglandin (PG) biosynthesis might increase the radioresponse of certain tumour cells. This study investigated specific PG binding sites, eicosanoid production as well as intracellular cAMP levels in cultured human hypernephroma cells derived from 11 patients upon nephrectomy. Scatchard analyses of the binding data revealed specific PGE1-, PGE2- as well as PGI2-binding sites (PGE1: Bmax = 755 +/- 206 fmol mg-1 protein, Kd = 3.7 +/- 2.7 nM PGE2: Bmax = 494 +/- 221 fmol mg-1 protein, Kd = 4.2 +/- 2.5 nM; PGI2: Bmax = 693 +/- 164 fmol mg-1 protein, Kd = 6.0 +/- 4.5 nM). Significant (P < 0.01) increase in PG binding sites expressed on human hypernephroma cells (PGE1: Bmax = 1084 +/- 303 fmol mg-1 protein, Kd = 2.8 +/- 1.3 nM; PGE2: Bmax = 663 +/- 309 fmol mg-1 protein, Kd = 2.2 +/- 1.5 nM; PGI2: Bmax = 1021 +/- 391 fmol/protein, Kd = 4.2 +/- 3.6 nM) and inhibition of PG biosynthesis (TXB2: -82.5%, PGE2: -87.5%. PGD2: -80.6%, PGF2: -81.3%) were found after acetylsalicylic acid (ASA)-treatment (0.5 mg 10(-6) cells for 24 h). Following irradiation (60Co, 1.0 Gy/min-1 over 10(min), PG binding sites (PGE1: Bmax = 266 +/- 153 fmol mg-1 protein, Kd = 5.0 +/- 5.0 nM; PGE2: Bmax = 148 +/- 66 fmol mg-1 protein, Kd = 4.7 +/- 3.6 nM; PGI2: Bmax = 325 +/- 194 fmol mg-1 protein, Kd = 6.8 +/- 7.1 nM) were significantly (P < 0.01) diminished. However, irradiation had no significant effect on PG binding sites in ASA-pretreated cells (PGE1: Bmax = 699 +/- 240 fmol mg-1 protein, Kd = 3.5 +/- 1.8 nM; iloprost: Bmax = 766 +/- 452 fmol mg-1 protein, Kd = 3.2 +/- 2.2 nM). Although there was no significant difference in the basal values for cAMP between control and ASA-treated group cells, the PG-induced cAMP-production was less pronounced in the control group. Taken together, the findings suggest that ASA may modify the radioresponse of cultured human hypernephroma cells by preventing the decrease of PG binding sites induced by irradiation.

摘要

有充分证据表明，前列腺素（PG）生物合成抑制剂可能会增加某些肿瘤细胞的放射反应。本研究调查了11例肾切除术后培养的人肾癌细胞中特定的PG结合位点、类花生酸生成以及细胞内cAMP水平。对结合数据进行Scatchard分析，发现了特异性的PGE1、PGE2以及PGI2结合位点（PGE1：Bmax = 755±206 fmol mg-1蛋白质，Kd = 3.7±2.7 nM；PGE2：Bmax = 494±221 fmol mg-1蛋白质，Kd = 4.2±2.5 nM；PGI2：Bmax = 693±164 fmol mg-1蛋白质，Kd = 6.0±4.5 nM）。乙酰水杨酸（ASA）处理（0.5 mg 10(-6)细胞，处理24小时）后，发现人肾癌细胞上表达的PG结合位点显著（P < 0.01）增加（PGE1：Bmax = 1084±303 fmol mg-1蛋白质，Kd = 2.8±1.3 nM；PGE2：Bmax = 663±309 fmol mg-1蛋白质，Kd = 2.2±1.5 nM；PGI2：Bmax = 1021±391 fmol/蛋白质，Kd = 4.2±3.6 nM），并且PG生物合成受到抑制（TXB2：-82.5%，PGE2：-87.5%，PGD2：-80.6%，PGF2：-81.3%）。照射（60Co，1.0 Gy/min-1，持续10分钟）后，PG结合位点（PGE1：Bmax = 266±153 fmol mg-1蛋白质，Kd = 5.0±5.0 nM；PGE2：Bmax = 148±66 fmol mg-1蛋白质，Kd = 4.7±3.6 nM；PGI2：Bmax = 325±194 fmol mg-1蛋白质，Kd = 6.8±7.1 nM）显著（P < 0.01）减少。然而，照射对ASA预处理细胞中的PG结合位点没有显著影响（PGE1：Bmax = 699±240 fmol mg-1蛋白质，Kd = 3.5±1.8 nM；伊洛前列素：Bmax = 766±452 fmol mg-1蛋白质，Kd = 3.2±2.2 nM）。虽然对照组和ASA处理组细胞之间cAMP的基础值没有显著差异，但对照组中PG诱导的cAMP生成不太明显。综上所述，这些发现表明ASA可能通过防止照射诱导的PG结合位点减少来改变培养的人肾癌细胞的放射反应。