Antiproliferative effects of β-blockers on human colorectal cancer cells
Antiproliferative effects of β-blockers on human colorectal cancer cells
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DOI：
10.3892/or.2015.3874
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发表时间：
2015-05-01
期刊：
影响因子：
4.2
通讯作者：
Ribeiro, L.
中科院分区：
文献类型：
--
作者：
Coelho, M.;Moz, M.;Ribeiro, L.
结肠癌是第四和第三最常见的癌症，分别在世界各地的男性和女性，其发病率正在上升。压力反应与癌症的发生和发展有关。儿茶酚胺（CA）、肾上腺素（AD）和去甲肾上腺素（NA）是应激反应的重要介质，通过与α-和β-肾上腺素能受体（AR）相互作用发挥其作用。结肠癌细胞表达β-AR，其激活与癌发生和肿瘤进展有关。关于β-AR阻滞剂作为癌症治疗的可能补充的功效的兴趣已经增加。本研究的目的是研究几种AR激动剂和β-受体阻滞剂对人结肠腺癌细胞系HT-29细胞增殖的影响。为此目的，HT-29细胞在不存在（对照）或存在AR-激动剂AD、NA和异丙肾上腺素（ISO）（0.1-100 μ M）的情况下温育12或24小时。测试的AR激动剂显示对HT-29细胞的增殖作用。为了研究几种β受体阻滞剂对AR激活诱导的细胞增殖的影响，用普萘洛尔处理细胞（PRO; 50 μ M），卡维地洛（CAR; 5 μ M），阿替洛尔（ATE; 50 μ M），或ICI 118，551（ICI; 5 μ M）孵育45分钟，然后同时与1 μ M和10 μ M的AR激动剂AD和ISO孵育。结果表明，肾上腺素能激活在结肠癌细胞增殖中起重要作用，最可能通过β-AR。所研究的β受体阻滞剂能够逆转AD和ISO诱导的增殖，其中一些阻滞剂显著降低HT-29细胞的增殖。阐明参与CA诱导的结肠癌细胞增殖的细胞内途径，以及β-受体阻滞剂逆转这种作用，可能有助于确定有前途的癌症治疗策略。
Colon cancer is the fourth and third most common cancer, respectively in men and women worldwide and its incidence is on the increase. Stress response has been associated with the incidence and development of cancer. The catecholamines (CA), adrenaline (AD) and noradrenaline (NA), are crucial mediators of stress response, exerting their effects through interaction with alpha- and beta-adrenergic receptors (AR). Colon cancer cells express beta-AR, and their activation has been implicated in carcinogenesis and tumor progression. Interest concerning the efficacy of beta-AR blockers as possible additions to cancer treatment has increased. The aim of this study was to investigate the effect of several AR agonists and beta-blockers following cell proliferation of HT-29 cells, a human colon adenocarcinoma cell line. For this purpose, HT-29 cells were incubated in the absence (control) or in the presence of the AR-agonists, AD, NA and isoprenaline (ISO) (0.1-100 mu M) for 12 or 24 h. The tested AR agonists revealed proliferative effects on HT-29 cells. In order to study the effect of several beta-blockers following proliferation induced by AR activation, the cells were treated with propranolol (PRO; 50 mu M), carvedilol (CAR; 5 mu M), atenolol (ATE; 50 mu M), or ICI 118,551 (ICI; 5 mu M) for 45 min prior, and simultaneously, to incubation with each of the AR agonists, AD and ISO, both at 1 and 10 mu M. The results suggested that adrenergic activation plays an important role in colon cancer cell proliferation, most probably through beta-AR. The beta-blockers under study were able to reverse the proliferation induced by AD and ISO, and some of these blockers significantly decreased the proliferation of HT-29 cells. The elucidation of the intracellular pathways involved in CA-induced proliferation of colon cancer cells, and in the reversion of this effect by beta-blockers, may contribute to identifying promising strategies in cancer treatment.