Department of Gastroenterology and Neurology, Kagawa University, Kagawa 761-0793, Japan.
Life Science Research Center, Kagawa University, Kagawa 761-0793, Japan.
Int J Mol Sci. 2019 Jun 29;20(13):3197. doi: 10.3390/ijms20133197.
Esophageal squamous cell carcinoma (ESCC) is the most common primary esophageal malignancy. Telmisartan, an angiotensin II type 1 (AT1) receptor blocker (ARB) and a widely used antihypertensive, has been shown to inhibit proliferation of various cancer types. This study evaluated the effects of telmisartan on human ESCC cell proliferation in vitro and in vivo and sought to identify the microRNAs (miRNAs) involved in these antitumor effects. We examined the effects of telmisartan on three human ESCC cell lines (KYSE150, KYSE180, and KYSE850). Telmisartan inhibited proliferation of these three cell lines by inducing S-phase arrest, which was accompanied by decreased expression of cyclin A2, cyclin-dependent kinase 2, and other cell cycle-related proteins. Additionally, telmisartan reduced levels of phosphorylated ErbB3 and thrombospondin-1 in KYSE180 cells. Furthermore, expression of miRNAs was remarkably altered by telmisartan in vitro. Telmisartan also inhibited tumor growth in vivo in a xenograft mouse model. In conclusion, telmisartan inhibited cell proliferation and tumor growth in ESCC cells by inducing cell-cycle arrest.
食管鳞状细胞癌(ESCC)是最常见的原发性食管恶性肿瘤。替米沙坦是一种血管紧张素 II 型 1(AT1)受体阻滞剂(ARB),也是一种广泛应用的降压药,已被证明可抑制多种癌症类型的增殖。本研究评估了替米沙坦在体外和体内对人 ESCC 细胞增殖的影响,并试图确定参与这些抗肿瘤作用的 microRNAs(miRNAs)。我们检查了替米沙坦对三种人 ESCC 细胞系(KYSE150、KYSE180 和 KYSE850)的影响。替米沙坦通过诱导 S 期阻滞抑制这三种细胞系的增殖,这伴随着细胞周期相关蛋白 cyclin A2、细胞周期蛋白依赖性激酶 2 等的表达降低。此外,替米沙坦还降低了 KYSE180 细胞中磷酸化 ErbB3 和血小板反应蛋白-1 的水平。此外,替米沙坦在体外还显著改变了 miRNA 的表达。替米沙坦还抑制了异种移植小鼠模型中的肿瘤生长。总之,替米沙坦通过诱导细胞周期阻滞抑制 ESCC 细胞的增殖和肿瘤生长。