Coelho M, Moz M, Correia G, Teixeira A, Medeiros R, Ribeiro L
Department of Biochemistry, Faculty of Medicine of The University of Porto, Porto, Portugal.
Molecular Oncology Group, Portuguese Institute of Oncology of Porto, Porto, Portugal.
Oncol Rep. 2015 May;33(5):2513-20. doi: 10.3892/or.2015.3874. Epub 2015 Mar 23.
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 α- and β-adrenergic receptors (AR). Colon cancer cells express β-AR, and their activation has been implicated in carcinogenesis and tumor progression. Interest concerning the efficacy of β-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 β-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 µM) for 12 or 24 h. The tested AR agonists revealed proliferative effects on HT-29 cells. In order to study the effect of several β-blockers following proliferation induced by AR activation, the cells were treated with propranolol (PRO; 50 µM), carvedilol (CAR; 5 µM), atenolol (ATE; 50 µM), or ICI 118,551 (ICI; 5 µM) for 45 min prior, and simultaneously, to incubation with each of the AR agonists, AD and ISO, both at 1 and 10 µM. The results suggested that adrenergic activation plays an important role in colon cancer cell proliferation, most probably through β-AR. The β-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 β-blockers, may contribute to identifying promising strategies in cancer treatment.
结肠癌分别是全球男性和女性中第四和第三常见的癌症，并且其发病率正在上升。应激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）是应激反应的关键介质，它们通过与α-和β-肾上腺素能受体（AR）相互作用发挥作用。结肠癌细胞表达β-AR，其激活与致癌作用和肿瘤进展有关。关于β-AR阻滞剂作为癌症治疗可能补充药物的疗效的关注度有所增加。本研究的目的是研究几种AR激动剂和β-阻滞剂对人结肠腺癌细胞系HT-29细胞增殖的影响。为此，将HT-29细胞在无（对照）或有AR激动剂AD、NA和异丙肾上腺素（ISO）（0.1 - 100 μM）的情况下孵育12或24小时。所测试的AR激动剂对HT-29细胞显示出增殖作用。为了研究几种β-阻滞剂对AR激活诱导的增殖的影响，在与每种AR激动剂AD和ISO（均为1和10 μM）孵育之前45分钟以及同时，用普萘洛尔（PRO；50 μM）、卡维地洛（CAR；5 μM）、阿替洛尔（ATE；50 μM）或ICI 118,551（ICI；5 μM）处理细胞。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，很可能是通过β-AR。所研究的β-阻滞剂能够逆转AD和ISO诱导的增殖，并且其中一些阻滞剂显著降低了HT-29细胞的增殖。阐明CA诱导结肠癌细胞增殖以及β-阻滞剂逆转这种作用所涉及的细胞内途径，可能有助于确定癌症治疗中有前景的策略。
