Regulation of prostate cancer cell growth and PSA expression by angiotensin II receptor blocker with peroxisome proliferator-activated receptor gamma ligand like action
Regulation of prostate cancer cell growth and PSA expression by angiotensin II receptor blocker with peroxisome proliferator-activated receptor gamma ligand like action
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DOI：
10.1002/pros.20571
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发表时间：
2007-06-15
期刊：
影响因子：
2.8
通讯作者：
Uemura, Hiroji
中科院分区：
文献类型：
--
作者：
Ishiguro, Hitoshi;Ishiguro, Yukari;Uemura, Hiroji
背景资料。我们先前报道血管紧张素II(AII)可促进前列腺癌细胞的增殖，其拮抗剂AT1R拮抗剂(ARB)在体内外均能抑制前列腺癌的增殖。在本研究中，我们研究了ARB替米沙坦是否具有作为PPAR-伽马(PPAR-γ)配体的独特功能，以及它对前列腺癌细胞的抑制作用。免疫印迹法检测丝裂原活化蛋白激酶(MAPK)的磷酸化、前列腺特异性抗原(PSA)和AT1R的表达。用PSA启动子和PPARγ反应元件(PPRE)载体进行荧光素酶活性检测。结果替米沙坦可抑制ARB细胞的增殖和信号转导。此外，Western印迹和荧光素酶分析证实替米沙坦抑制PSA的表达，表明ARB在前列腺癌细胞中的作用类似于抗雄激素药物。结论：本研究表明ARB，特别是那些具有PPARγ配体样结构的ARB，对雄激素依赖和非雄激素依赖的前列腺癌具有潜在的拮抗作用。
BACKGROUND. We previously reported that angiotensin II (AII) activated the proliferation of Prostate cancer cells, and its antagonist, an AII receptor type 1 (AT1R) blocker (ARB), inhibited the proliferation of prostate cancer in vitro and in vivo. In the present study, we investigated whether telmisartan, an ARB, has a unique feature as a peroxisome proliferator-activated receptor gamma (PPAR-gamma) ligand, and its suppressive potential on prostate cancer cells.METHODS. Cell count or MTT assay were carried out for growth suppression of prostate cancer cells. Phosphorylation of mitogen-activated protein kinase (MAPK), specific expression of prostate specific antigen (PSA) and AT1R were investigated by western blot. To confirm the PPAR gamma activity of ARBs, luciferase assay using PSA promoter and PPAR gamma response elements (PPRE) plasmids was performed.RESULTS. The results showed that cell proliferation and signal transduction were inhibited by telmisartan treatment. Also, inhibition of PSA expression by telmisartan was confirmed by western blot and luciferase assay, indicating that an ARB acted in a similar way such as an anti-androgenic agent in prostate cancer cells.CONCLUSION. The present study showed ARBs, especially those possessing a PPAR gamma ligand-like structure, have a potential antagonistic effect on androgen-dependent and -independent prostate cancer.