Telmisartan is a potent target for prevention and treatment in human prostate cancer
Telmisartan is a potent target for prevention and treatment in human prostate cancer
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DOI：
10.3892/or_00000006
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发表时间：
2008-08-01
期刊：
影响因子：
4.2
通讯作者：
Yoshimura, Rikio
中科院分区：
文献类型：
--
作者：
Funao, Kiyoaki;Matsuyama, Masahide;Yoshimura, Rikio
血管紧张素II受体阻滞剂(ARBs)是广泛使用的高血压治疗剂。最近的研究表明，ARB 具有抑制前列腺癌细胞 (PC) 生长的潜力。此外，最近有报道称替米沙坦（ARB的一种）具有过氧化物酶体增殖物激活受体（PPAR）-γ激活作用。我们之前报道过 PPAR-γ 配体通过凋亡诱导 PC 细胞生长停滞。在这项研究中，我们评估了替米沙坦和其他 ARB 对几种 PC 细胞系细胞增殖的影响。我们使用正常前列腺基质细胞 (NPC)、人类激素难治性 PC (PC3)、雄激素非依赖性 PC (DU-145) 和雄激素依赖性 PC (LNCaP) 细胞系。通过 MTT 法检测替米沙坦和其他 ARB（坎地沙坦、缬沙坦、厄贝沙坦和氯沙坦）对 PC 细胞生长的影响。使用流式细胞术和Hoechst染色来确定ARB是否诱导细胞凋亡。替米沙坦以浓度依赖性和时间依赖性方式对 PC 细胞产生显着抑制。用100μM替米沙坦处理的PC细胞诱导早期细胞凋亡和DNA断裂。然而，用100μM替米沙坦处理的NPC并没有诱导细胞凋亡或DNA断裂。此外，其他ARB对PC细胞和NPC的细胞增殖没有影响。替米沙坦可能通过 PPAR-γ 介导针对 PC 细胞的有效抗增殖作用。因此，替米沙坦是预防和治疗 PC 的有效靶点。
Angiotensin II receptor blockers (ARBs) are widely used Lis hypertensive therapeutic agent. Recent studies have reported that ARBs have the potential to inhibit the growth of prostate cancer (PC) cells. Moreover, it was recently reported that Telmisartan (a kind of ARB) has peroxisome proliferator-activated receptor (PPAR)-gamma activation. We previously reported that PPAR-gamma ligand induces growth arrest of PC cells through apoptosis. In this study, we evaluated the effects of the Telmisartan and other ARBs on cell proliferation in several PC cell lines. We used normal prostate stromal cell (NPC), human hormone-refractory PC (PC3), androgen-independent PC (DU-145) and androgen-dependent PC (LNCaP) cell lines. Effects of Telmisartan and other ARBs (Candesartan, Valsartan, Irbesartan and Losartan) on PC cell growth were examined by MTT assay. Flow cytometry and Hoechst staining were used to determine whether or not ARBs induce apoptosis. Telmisartan caused marked inhibition of PC cells in concentration-dependent and time-dependent manner. PC cells with treatment of 100 mu M Telmisartan induced early apoptosis and DNA fragmentation. However, NPC with treatment of 100 mu M Telmisartan did not induce apoptosis or DNA fragmentation. Furthermore, other ARBs had no effect on cell proliferation in the PC cells and NPC. Telmisartan may mediate potent antiproliferative effects against PC cells through PPAR-gamma. Thus, Telmisartan is a potent target for prevention and treatment in PC.