Evaluation of SD-208, a TGF-β-RI Kinase Inhibitor, as an Anticancer Agent in Retinoblastoma.
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.
Department of Biochemistry and Genetics, Molecular and Medicine Research Center, Arak University of Medical Sciences, Arak, Iran.
Puran
P
Fadakar
Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran.
Abolfazl
A
Akbari
Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Fariba
F
Ghassemi
Medical Plants Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Gholam Reza
GR
Mobini
Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Masoumeh
M
Mohebi
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Manzar
M
Bolhassani
Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Hoda
H
Abed Khojasteh
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. AND Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Mansour
M
Heidari
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics; D011621:Pteridines / Q000494:pharmacology*; D012334:RNA, Neoplasm / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D019572:Retinal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D012175:Retinoblastoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors*
C524941:MIRN17 microRNA, human; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D011621:Pteridines; D012334:RNA, Neoplasm; C511004:SD-208; D016212:Transforming Growth Factor beta
Retinoblastoma; SD-208; Y-79 cell line; miRNA