Matsuyama Masahide, Funao Kiyoaki, Kuratsukuri Katsuyuki, Tanaka Tomoaki, Kawahito Yutaka, Sano Hajime, Chargui Jamel, Touraine Jean-Louis, Yoshimura Norio, Yoshimura Rikio
Department of Transplantation and Clinical Immunology, Claude Bernard University of Lyon and Lyon Hospitals, Lyon, France ;
Exp Ther Med. 2010 Mar;1(2):301-306. doi: 10.3892/etm_00000046. Epub 2010 Mar 1.
Angiotensin II receptor blockers (ARBs) are widely used as hypertensive therapeutic agents. In addition, studies have provided evidence that ARBs have the potential to inhibit the growth of several types of cancer cells. It was reported that telmisartan (a type of ARB) has peroxisome proliferator-activated receptor (PPAR)-γ activation activity. We previously reported that the PPAR-γ ligand induces growth arrest in human urological cancer cells through apoptosis. In this study, we evaluated the effects of telmisartan and other ARBs on cell proliferation in renal cell carcinoma (RCC), bladder cancer (BC), prostate cancer (PC) and testicular cancer (TC) cell lines. The inhibitory effects of telmisartan and other ARBs (candesartan, valsartan, irbesartan and losartan) on the growth of the RCC, BC, PC and TC cell lines was investigated using an MTT assay. Flow cytometry and Hoechst staining were used to determine whether the ARBs induced apoptosis. Telmisartan caused marked growth inhibition in the urological cancer cells in a dose- and time-dependent manner. Urological cancer cells treated with 100 μM telmisartan underwent early apoptosis and DNA fragmentation. However, the other ARBs had no effect on cell proliferation in any of the urological cancer cell lines. Telmisartan may mediate potent anti-proliferative effects in urological cancer cells through PPAR-γ. Thus, telmisartan is a potent target for the prevention and treatment of human urological cancer.
血管紧张素 II 受体阻滞剂（ARBs）被广泛用作高血压治疗药物。此外，研究已提供证据表明 ARBs 有抑制多种癌细胞生长的潜力。据报道，替米沙坦（一种 ARB）具有过氧化物酶体增殖物激活受体（PPAR）-γ 激活活性。我们之前报道过 PPAR-γ 配体通过凋亡诱导人泌尿系统癌细胞生长停滞。在本研究中，我们评估了替米沙坦和其他 ARBs 对肾细胞癌（RCC）、膀胱癌（BC）、前列腺癌（PC）和睾丸癌（TC）细胞系细胞增殖的影响。使用 MTT 法研究了替米沙坦和其他 ARBs（坎地沙坦、缬沙坦、厄贝沙坦和氯沙坦）对 RCC、BC、PC 和 TC 细胞系生长的抑制作用。采用流式细胞术和 Hoechst 染色来确定 ARBs 是否诱导凋亡。替米沙坦以剂量和时间依赖性方式显著抑制泌尿系统癌细胞的生长。用 100 μM 替米沙坦处理的泌尿系统癌细胞发生早期凋亡和 DNA 片段化。然而，其他 ARBs 对任何泌尿系统癌细胞系的细胞增殖均无影响。替米沙坦可能通过 PPAR-γ 在泌尿系统癌细胞中介导强大的抗增殖作用。因此，替米沙坦是预防和治疗人类泌尿系统癌症的有力靶点。
