Effects of adrenaline in human colon adenocarcinoma HT-29 cells
Effects of adrenaline in human colon adenocarcinoma HT-29 cells
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DOI：
10.1016/j.lfs.2011.04.007
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发表时间：
2011-06-20
期刊：
影响因子：
6.1
通讯作者：
Cho, Chi Hin
中科院分区：
文献类型：
--
作者：
Wong, Helen P. S.;Ho, Judy W. C.;Cho, Chi Hin
目的：压力与癌症的发展有关。肾上腺素水平在应激反应中增加。肾上腺素对结肠癌的影响在很大程度上是未知的。本研究旨在探讨肾上腺素对人结肠腺癌HT-29细胞增殖的影响及其可能的作用机制，主要方法：采用[H-3]胸苷掺入法测定肾上腺素对HT-29细胞增殖的影响。Western blot检测细胞中环氧合酶2（考克斯2）和血管内皮生长因子（VEGF）的表达。用酶谱法和酶免疫法分别测定基质金属蛋白酶-9（MMP-9）活性和前列腺素E-2（PGE（2））释放。HT-29细胞中考克斯-2和VEGF表达增强。肾上腺素还可上调MMP-9活性和PGE（2）释放。肾上腺素刺激HT-29细胞增殖，考克斯-2抑制剂sc-236可逆转肾上腺素刺激的HT-29细胞增殖。考克斯-2抑制剂也逆转肾上腺素对VEGF表达和MMP-9活性的作用。进行进一步研究以确定β-肾上腺素受体的参与。肾上腺素对结肠癌生长的刺激作用分别被阿替洛尔和ICI 118，551（一种β（1）和β（2）选择性拮抗剂）阻断。这表明β-肾上腺素受体在这一过程中的作用。结果表明，肾上腺素通过β 1和β 2肾上腺素受体，通过考克斯2依赖性途径刺激HT-29细胞增殖，并抑制HT-29细胞中考克斯2、VEGF表达、MMP-9活性和PGE（2）释放。(C)2011 Elsevier Inc. All rights reserved.
Aims: Stress has been implicated in the development of cancers. Adrenaline levels are increased in response to stress. The effects of adrenaline on colon cancer are largely unknown. The aims of the study are to determine the effects of adrenaline in human colon adenocarcinoma HT-29 cells and the possible underlying mechanisms involved.Main methods: The effect of adrenaline on HT-29 cell proliferation was determined by [H-3] thymidine incorporation assay. Expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) were detected by Western blot. Matrix metalloproteinase-9 (MMP-9) activity and prostaglandin E-2 (PGE(2)) release were determined by zymography and enzyme immunoassay, respectively.Key findings: Adrenaline stimulated HT-29 cell proliferation. This was accompanied by the enhanced expression of COX-2 and VEGF in HT-29 cells. Adrenaline also upregulated MMP-9 activity and PGE(2) release. Adrenaline stimulated HT-29 cell proliferation which was reversed by COX-2 inhibitor sc-236. COX-2 inhibitor also reverted the action of adrenaline on VEGF expression and MMP-9 activity. Further study was performed to determine the involvement of beta-adrenoceptors. The stimulatory action of adrenaline on colon cancer growth was blocked by atenolol and ICI 118,551, a beta(1)- and beta(2)-selective antagonist, respectively. This signified the role of beta-adrenoceptors in this process. In addition, both antagonists also abrogated the stimulating actions of adrenaline on COX-2, VEGF expression, MMP-9 activity and PGE(2) release in HT-29 cells.Significance: These results suggest that adrenaline stimulates cell proliferation of HT-29 cells via both beta(1)- and beta(2)-adrenoceptors by a COX-2 dependent pathway. (C) 2011 Elsevier Inc. All rights reserved.