Beta-Adrenoceptor Action on Pancreatic Cancer Cell Proliferation and Tumor Growth in Mice
Beta-Adrenoceptor Action on Pancreatic Cancer Cell Proliferation and Tumor Growth in Mice
复制标题
β-肾上腺素受体对小鼠胰腺癌细胞增殖和肿瘤生长的作用
DOI：
10.5754/hge11271
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发表时间：
2012-03-01
影响因子：
--
通讯作者：
Huang, Jian
中科院分区：
文献类型：
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作者：
Lin, Xueping;Luo, Kai;Huang, Jian
背景/目的：越来越多的证据表明某些癌症进展与β-肾上腺素受体（β-AR）密切相关。然而，对β-AR介导的胰腺癌细胞增殖的潜在机制知之甚少。在本研究中，我们评估了beta-ARs对人胰腺导管腺癌（PDAC）细胞系Panc-1增殖的可能功能，并探讨了beta-ARs介导的下游信号通路。方法学：采用免疫荧光法、Western blot法、BrdU掺入法和裸鼠移植瘤生长法，对胰腺癌细胞Panc-1进行β 1和β 2 AR的表达、β AR介导的下游信号通路激活以及体内外细胞增殖实验。结果如下：非选择性β-AR激动剂异丙肾上腺素（ISO）以剂量依赖性方式通过β-AR显著增加Panc-1细胞的增殖，同时激活ERK/MAPK信号通路。ISO可增加Panc-1细胞磷酸化ERK的表达水平。此外，体内研究表明，ISO促进异种移植肿瘤生长，并且这种作用被非选择性β-AR拮抗剂（β-阻断剂）普萘洛尔（PRO）治疗所抑制。结论：这些发现表明，PDAC的发生和进展受到ISO和PRO的显著调节，PRO治疗可能有助于PDAC的标记物引导的癌症干预。因此，PRO具有高度的特异性，有望成为治疗和干预PDAC的新药。
Background/Aims: There is growing evidence that some cancer progression is closely associated with beta-adrenoreceptors (beta-ARs). However, the underlying mechanisms for beta-ARs mediated proliferation of pancreatic cancer cell are poorly understood. In the current study, we evaluated the possible function of beta-ARs on the proliferation of human pancreatic ductal adenocarcinomas (PDAC) cell line Panc-1 and explored beta-ARs-mediated downstream signal pathway. Methodology: Series of experiments, such as expression of beta 1- and beta 2-ARs on pancreatic cancer cell line Panc-1, beta-ARs-mediated downstream signal pathway activation as well as cell proliferation assay in vitro and in vivo were performed with immunofluorescence, Western blot analysis, BrdU incorporation assays and xenograft tumor growth respectively. Results: Non-selective beta-ARs agonist Isoproterenol (ISO) significantly increased cell proliferation via beta-ARs in a dose-dependent manner, with concomitant activation of ERK/MAPK signal pathway in Panc-1 cells. ISO increased expression level of phosphorylated ERK in Panc-1 cells. Furthermore, in vivo study showed that ISO enhanced xenograft tumor growth and this effect was suppressed by non-selective beta-ARs antagonist (beta-blocker), propranolol (PRO) treatment. Conclusions: These findings suggest that the development and progression of PDAC is subject to significant modulation by ISO and PRO and the treatment with PRO may be useful for marker-guided cancer intervention of PDAC. Therefore, PRO may be developed a novel drug for the treatment and intervention of PDAC for its high specificity.