Akbari Abolfazl, Ghahremani Mohammad Hossein, Mobini Gholam Reza, Abastabar Mahdi, Akhtari Javad, Bolhassani Manzar, Heidari Mansour
Colorectal Research Center, Rasoul-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Iran J Basic Med Sci. 2015 Sep;18(9):856-61.
Transforming growth factor-β (TGF-β) is involved in colorectal cancer (CRC). The SD-208 acts as an anti-cancer agent in different malignancies via TGF-β signaling. This work aims to show the effect of manipulation of TGF-β signaling on some miRNAs implicated in CRC.
We investigated the effects of SD-208 on SW-48, a colon adenocarcinoma cell line. The cell line was treated with 0.5, 1 and 2 μM concentrations of SD-208. Then, the xenograft model of colon cancer was established by subcutaneous inoculation of SW-48 cell line into the nude mice. The animals were treated with SD-208 for three weeks. A quantitative real-time PCR was carried out for expression level analysis of selected oncogenic (miR-21, 31, 20a and 135b) and suppressor-miRNAs (let7-g, miR-133b, 145 and 200c). Data were analyzed using the 2-∆∆CT method through student's t-test via the GraphPad Prism software.
Our results revealed that SD-208 could significantly down-regulate the expression of one key onco-miRNA, miR-135b, in either SW-48 colon cells (P=0.006) or tumors orthotopically implanted in nude mice (P=0.018). Our in silico study also predicted that SD-208 could modulate the expression of potential downstream tumor suppressor targets of the miR135b.
Our data provide novel evidence that anticancer effects of SD-208 (and likely other TGF-β inhibitors) may be owing to their ability to regulate miRNAs expression.
转化生长因子-β（TGF-β）与结直肠癌（CRC）有关。SD-208通过TGF-β信号通路在不同恶性肿瘤中发挥抗癌作用。本研究旨在揭示调控TGF-β信号通路对一些与CRC相关的微小RNA（miRNA）的影响。
我们研究了SD-208对结肠腺癌细胞系SW-48的作用。该细胞系分别用0.5、1和2 μM浓度的SD-208处理。然后，通过将SW-48细胞系皮下接种到裸鼠体内建立结肠癌异种移植模型。动物用SD-208治疗三周。对选定的致癌性（miR-21、31、20a和135b）和抑癌miRNA（let7-g、miR-133b、145和200c）进行定量实时PCR以分析其表达水平。数据通过GraphPad Prism软件采用学生t检验的2-∆∆CT法进行分析。
我们的结果显示，SD-208可显著下调一种关键致癌miRNA miR-135b在SW-48结肠细胞（P = 0.006）或原位植入裸鼠的肿瘤中的表达（P = 0.018）。我们的计算机模拟研究还预测SD-208可调节miR135b潜在下游肿瘤抑制靶点的表达。
我们的数据提供了新的证据，表明SD-208（可能还有其他TGF-β抑制剂）的抗癌作用可能归因于它们调节miRNA表达的能力。
