Department of Pathology, The Affiliated Hospital of Medical College, Qingdao University, 16 Jiangsu Road, Qingdao, Shandong 266003, China.
Neuropeptides. 2011 Apr;45(2):151-6. doi: 10.1016/j.npep.2011.01.002. Epub 2011 Jan 26.
The presence of neurotensin and neurotensin receptors has been demonstrated in human pancreatic carcinomas using autoradiography and Northern blot analysis. In vitro studies have reported that the neurotensin antagonist SR 48692 could inhibit the growth of MIA PaCa-2 cells in a neurotensin mediated fashion, and neurotensin could overcome this inhibition or stimulate proliferation. However, it is currently unknown whether such actions are exerted on PANC-1 cells. In addition, the immunolocation of neurotensin and neurotensin receptors is still unclear in human pancreatic ductal carcinoma tissues. Immunohistochemistry was applied to detect the distribution of neurotensin and neurotensin receptor subtype-1 in human pancreatic ductal carcinoma and normal pancreatic tissues. Furthermore, an in vitro study was carried out to test the pharmacological profile of neurotensin and SR 48692 in human pancreatic ductal carcinoma cell line PANC-1. Compared with normal pancreatic tissues, pancreatic ductal carcinoma tissues have higher neurotensin and neurotensin receptor subtype-1 expression rates. Pancreatic ductal carcinomas (32/40) bear the expression of both neurotensin and neurotensin receptor subtype-1. We observed that neurotensin (10⁻¹¹-10⁻⁷ M) significantly stimulated the proliferation of PANC-1 and SR 48692 (10⁻¹¹-10⁻⁷ M) alone had no effect on the growth of PANC-1 cells; however, SR 48692 (10⁻¹⁰-10⁻⁶ M) inhibited the stimulatory effect of neurotensin (10⁻⁹ M). Considering the overexpression of both neurotensin and neurotensin receptor subtype-1 in pancreatic ductal carcinomas, it could enable us to develop markers for pancreatic cancer diagnosis. As SR 48692 could inhibit neurotensin induced cell growth, neurotensin receptor subtype-1 may serve as a therapeutic target for the therapy of pancreatic carcinomas. Furthermore, our study indicates that the counteraction of neurotensin and neurotensin receptor subtype-1 regulates the genesis and development of pancreatic carcinomas.
神经降压素及其受体在人类胰腺癌中通过放射自显影和 Northern blot 分析得以证实。体外研究报告称，神经降压素拮抗剂 SR 48692 可以以神经降压素介导的方式抑制 MIA PaCa-2 细胞的生长，而神经降压素可以克服这种抑制或刺激增殖。然而，目前尚不清楚这些作用是否在 PANC-1 细胞上发挥。此外，神经降压素和神经降压素受体亚型-1在人类胰腺导管腺癌组织中的免疫定位仍然不清楚。应用免疫组织化学检测神经降压素和神经降压素受体亚型-1在人类胰腺导管腺癌和正常胰腺组织中的分布。此外，进行了一项体外研究，以测试神经降压素和 SR 48692 在人胰腺导管癌细胞系 PANC-1 中的药理学特征。与正常胰腺组织相比，胰腺导管腺癌组织具有更高的神经降压素和神经降压素受体亚型-1表达率。胰腺导管腺癌（32/40）具有神经降压素和神经降压素受体亚型-1的双重表达。我们观察到神经降压素（10⁻¹¹-10⁻⁷ M）显著刺激 PANC-1 的增殖，而 SR 48692（10⁻¹¹-10⁻⁷ M）单独对 PANC-1 细胞的生长没有影响；然而，SR 48692（10⁻¹⁰-10⁻⁶ M）抑制了神经降压素（10⁻⁹ M）的刺激作用。鉴于神经降压素和神经降压素受体亚型-1在胰腺导管腺癌中的过度表达，这可能使我们能够开发用于胰腺癌诊断的标志物。由于 SR 48692 可以抑制神经降压素诱导的细胞生长，因此神经降压素受体亚型-1可以作为治疗胰腺癌的治疗靶点。此外，我们的研究表明，神经降压素和神经降压素受体亚型-1的拮抗作用调节了胰腺癌的发生和发展。
