Department of Comparative Endocrinology, Faculty of Biomedical Sciences and Postgraduate Training, Medical University of Lodz, Poland.
Arch Med Sci. 2013 Aug 30;9(4):739-44. doi: 10.5114/aoms.2012.30955. Epub 2012 Oct 8.
Caveolin-1, the major structural protein of caveolae, interacts directly with the AT1 receptor. The biological functions of caveolin-1 in cancer are compound, multifaceted, and depend on cell type, tumour grade and cancer stage. The AT1-R-caveolin complex in caveolae may coordinate angiotensin II (Ang II) induced signalling. The aim of this study was to determine the effect of the angiotensin II receptor type 1 blocker candesartan on caveolin expression in human metastatic prostate adenocarcinoma cells PC-3.
WST-1 and BrdU assays were used as indicators of cell viability and proliferation after angiotensin II and/or candesartan stimulation. Real-time RT-PCR and western blot were used to study the effect of Ang II and/or candesartan on the expression of Cav-1 and AT1-R in PC-3 cells.
We found that the expression of caveolin-1 mRNA in the PC-3 cells treated with CV was significantly decreased in comparison with the control (2.9 ±0.17, 4.7 ±0.6, p < 0.05), whereas a higher caveolin-1 mRNA expression was observed in those after Ang II treatment (6.0 ±0.43, 4.7 ±0.6, p < 0.05). Protein analysis indicate that the expression of caveolin-1 protein in the PC-3 cells treated with candesartan was significantly decreased when compared with the control (0.69 ±0.05, 1.6 ±0.12, p < 0.05), whereas higher caveolin-1 protein expression was observed after Ang II treatment (2.5 ±0.20, 1.6 ±0.12, p < 0.05).
These results provide new information on the action of candesartan and may improve the knowledge about AT1 receptor inhibitors, which can be potentially useful in prostate cancer therapy.
窖蛋白-1 是质膜窖的主要结构蛋白，可直接与 AT1 受体相互作用。窖蛋白-1 在癌症中的生物学功能是复杂的、多方面的，并且取决于细胞类型、肿瘤分级和癌症阶段。窖质膜中的 AT1-R-窖蛋白复合物可能协调血管紧张素 II（Ang II）诱导的信号转导。本研究旨在确定血管紧张素 II 受体 1 型阻滞剂坎地沙坦对人转移性前列腺腺癌 PC-3 细胞窖蛋白表达的影响。
WST-1 和 BrdU 测定分别作为血管紧张素 II 和/或坎地沙坦刺激后细胞活力和增殖的指标。实时 RT-PCR 和 Western blot 用于研究 Ang II 和/或坎地沙坦对 PC-3 细胞 Cav-1 和 AT1-R 表达的影响。
我们发现，与对照组相比，用 CV 处理的 PC-3 细胞中窖蛋白-1 mRNA 的表达明显降低（2.9 ±0.17，4.7 ±0.6，p <0.05），而 Ang II 处理后观察到更高的窖蛋白-1 mRNA 表达（6.0 ±0.43，4.7 ±0.6，p <0.05）。蛋白分析表明，与对照组相比，用坎地沙坦处理的 PC-3 细胞中窖蛋白-1 蛋白的表达明显降低（0.69 ±0.05，1.6 ±0.12，p <0.05），而 Ang II 处理后观察到更高的窖蛋白-1 蛋白表达（2.5 ±0.20，1.6 ±0.12，p <0.05）。
这些结果提供了坎地沙坦作用的新信息，并可能提高对 AT1 受体抑制剂的认识，这对前列腺癌治疗可能是有用的。
