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TGF-β-RI激酶抑制剂SD-208作为视网膜母细胞瘤抗癌药物的评估

Evaluation of SD-208, a TGF-β-RI Kinase Inhibitor, as an Anticancer Agent in Retinoblastoma.

作者信息

Fadakar Puran, Akbari Abolfazl, Ghassemi Fariba, Mobini Gholam Reza, Mohebi Masoumeh, Bolhassani Manzar, Abed Khojasteh Hoda, Heidari Mansour

机构信息

Department of Biochemistry and Genetics, Molecular and Medicine Research Center, Arak University of Medical Sciences, Arak, Iran.

Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran.

出版信息

Acta Med Iran. 2016 Jun;54(6):352-8.

Abstract

Retinoblastoma is the most common intraocular tumor in children resulting from genetic alterations and transformation of mature retinal cells. The objective of this study was to investigate the effects of SD-208, TGF-β-RI kinase inhibitor, on the expression of some miRNAs including a miR-17/92 cluster in retinoblastoma cells. Prior to initiate this work, the cell proliferation was studied by Methyl Thiazolyl Tetrazolium (MTT) and bromo-2'-deoxyuridine (BrdU) assays. Then, the expression patterns of four miRNAs (18a, 20a, 22, and 34a) were investigated in the treated SD-208 (0.0, 1, 2 and 3 µM) and untreated Y-79 cells. A remarkable inhibition of the cell proliferation was found in Y-79 cells treated with SD-208 versus untreated cells. Also, the expression changes were observed in miRNAs 18a, 20a, 22 and 34a in response to SD-208 treatment (P<0.05). The findings of the present study suggest that the anti-cancer effect of SD-208 may be exerted due to the regulation of specific miRNAs, at least in this particular retinoblastoma cell line. To the best of the researchers' knowledge, this is the first report demonstrating that the SD-208 could alter the expression of tumor suppressive miRNAs as well as oncomiRs in vitro. In conclusion, the present data suggest that SD-208 could be an alternative agent in retinoblastoma treatment.

摘要

视网膜母细胞瘤是儿童中最常见的眼内肿瘤,由成熟视网膜细胞的基因改变和转化引起。本研究的目的是探讨TGF-β-RI激酶抑制剂SD-208对视网膜母细胞瘤细胞中包括miR-17/92簇在内的一些微小RNA(miRNA)表达的影响。在开展这项工作之前,通过甲基噻唑基四氮唑(MTT)和溴脱氧尿苷(BrdU)试验研究了细胞增殖情况。然后,在经SD-208(0.0、1、2和3μM)处理和未处理的Y-79细胞中研究了四种miRNA(18a、20a、22和34a)的表达模式。与未处理的细胞相比,用SD-208处理的Y-79细胞中发现细胞增殖受到显著抑制。此外,在SD-208处理后,miRNA 18a、20a、22和34a的表达发生了变化(P<0.05)。本研究结果表明,SD-208的抗癌作用可能是由于对特定miRNA的调控,至少在这种特定的视网膜母细胞瘤细胞系中是如此。据研究人员所知,这是第一份证明SD-208在体外可改变肿瘤抑制性miRNA以及癌基因miRNA表达的报告。总之,目前的数据表明SD-208可能是视网膜母细胞瘤治疗中的一种替代药物。

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