Involvement of a2-and ß2-adrenoceptors on breast cancer cell proliferation and tumour growth regulation
Involvement of a2-and ß2-adrenoceptors on breast cancer cell proliferation and tumour growth regulation
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DOI：
10.1111/j.1476-5381.2011.01791.x
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发表时间：
2012-05-01
影响因子：
7.3
通讯作者：
Luethy, I. A.
中科院分区：
文献类型：
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作者：
Perez Pinero, C.;Bruzzone, A.;Luethy, I. A.
背景和技术β-肾上腺素受体在人类和实验动物乳腺癌细胞中表达。然而，报道的激动剂和拮抗剂对细胞增殖和肿瘤生长的影响是矛盾的，排除了它们作为可能的辅助治疗的利用，主要是在难治性tumors.Experimental方法的情况下β-肾上腺素受体的表达进行了分析，通过免疫荧光和RT-PCR。通过[H-3]胸苷掺入评估细胞增殖，通过卡尺测量肿瘤生长，通过蛋白质印迹法评估ERK 1/2磷酸化。肾上腺素（通过α（2）-肾上腺素能受体作用）可增加细胞增殖，β-肾上腺素能受体激动剂异丙肾上腺素和β（2）-肾上腺素能受体激动剂沙丁胺醇可降低每个试验细胞系的细胞增殖。异丙肾上腺素和沙丁胺醇在每种测试的肿瘤中减少肿瘤生长（在裸鼠中作为异种移植物生长的小鼠C4-HD和CC 4 -3-HI以及人IBH-4、IBH-6和MDA-MB-231细胞系）。这些作用被β-肾上腺素受体拮抗剂普萘洛尔逆转。β 2-肾上腺素受体拮抗剂rauwolscine和β 2-肾上腺素受体激动剂沙丁胺醇在抑制肿瘤生长方面同样有效。在IBH-4肿瘤中分析的ERK 1/2活化与肿瘤生长相关，β-肾上腺素受体激动剂降低其活化。抑制ERK 1/2磷酸化在体外主要介导的PKA pathway.CONCLUSIONS AND IMPLICATIONS在我们的实验模型中，β-肾上腺素受体激动剂抑制乳腺癌细胞增殖和肿瘤生长，可能介导的抑制ERK 1/2磷酸化。β-肾上腺素受体激动剂与β-肾上腺素受体拮抗剂萝芙木碱一样有效，为乳腺癌提供了可能的新辅助治疗。
BACKGROUND AND PURPOSEbeta-Adrenoceptors are expressed in human and experimental animal breast cancer cells. However, the effect of the agonists and antagonists reported on cell proliferation and tumour growth was paradoxical, precluding their utilization as possible adjuvant therapy, mainly in the cases of refractory tumours.EXPERIMENTAL APPROACHbeta-Adrenoceptor expression was analysed by immunofluorescence and RT-PCR. Cell proliferation was assessed by [H-3]thymidine incorporation, tumour growth by measuring with a calliper and ERK 1/2 phosphorylation by Western blotting.KEY RESULTSbeta(2)-Adrenoceptor expression was confirmed in the mouse and human cells tested. Cell proliferation was increased by adrenaline (by alpha(2)-adrenoceptor action) and decreased in every tested cell line by the beta-adrenoceptor agonist isoprenaline and the beta(2)-adrenoceptor agonist salbutamol. Isoprenaline and salbutamol reduced tumour growth in every tumour tested (mouse C4-HD and CC4-3-HI and human IBH-4, IBH-6 and MDA-MB-231 cell lines growing as xenografts in nude mice). These effects were reversed by the beta-adrenoceptor antagonist propranolol. The beta(2)-adrenoceptor antagonist rauwolscine and the beta(2)-adrenoceptor agonist salbutamol were equally effective in diminishing tumour growth. ERK 1/2 activation analysed in IBH-4 tumours correlated with tumour growth, with the b-adrenoceptor agonists decreasing its activation. Inhibition of ERK 1/2 phosphorylation in vitro was mainly mediated by the PKA pathway.CONCLUSIONS AND IMPLICATIONSIn our experimental models, the b-adrenoceptor agonists inhibited breast cancer cell proliferation and tumour growth, probably mediated by inhibition of ERK 1/2 phosphorylation. The b-adrenoceptor agonists were as effective as the beta-adrenoceptor antagonist rauwolscine, providing possible novel adjuvant treatments for breast cancer.