The effect of combined miR-200c replacement and cisplatin on apoptosis induction and inhibition of gastric cancer cell line migration.

Autor: Ghasabi M; Immunology Research Center, TabrizUniversity of Medical Sciences, Tabriz, Iran., Majidi J; Immunology Research Center, TabrizUniversity of Medical Sciences, Tabriz, Iran., Mansoori B; Immunology Research Center, TabrizUniversity of Medical Sciences, Tabriz, Iran.; Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark.; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran., Mohammadi A; Aging Research Institute, Physical Medicine and Rehabilitation Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Shomali N; Immunology Research Center, TabrizUniversity of Medical Sciences, Tabriz, Iran., Shirafkan N; Immunology Research Center, TabrizUniversity of Medical Sciences, Tabriz, Iran., Baghbani E; Immunology Research Center, TabrizUniversity of Medical Sciences, Tabriz, Iran., Kazemi T; Immunology Research Center, TabrizUniversity of Medical Sciences, Tabriz, Iran., Baradaran B; Immunology Research Center, TabrizUniversity of Medical Sciences, Tabriz, Iran.
Jazyk: angličtina
Zdroj: Journal of cellular physiology [J Cell Physiol] 2019 Dec; Vol. 234 (12), pp. 22581-22592. Date of Electronic Publication: 2019 May 20.
DOI: 10.1002/jcp.28823
Abstrakt: One of the major obstacles in the treatment of cancer is resistance to standard chemotherapeutic drugs. According to the numerous reports, miR-200c is involved in many cancers, especially gastric cancer, and also miR-200c has been known as an effective factor in the elimination of chemotherapy resistance. The purpose of this study was to explore the potential function and mechanism of miR-200c and cisplatin in the inhibition of migration and induction of apoptosis in gastric cancer cells. In this study, first, miR-200c mimics and LNA-anti-miR-200c were transfected into KATOIII cells. Moreover, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay results revealed that increased miR-200c expression and cisplatin can more inhibited the proliferation of KATOIII cells. MiR-200c overexpression inhibited the movement of KATOIII cells in wound healing assay. Subsequently, miR-200c/cisplatin could suppress colony formation in KATOIII cells. To identify a potential miR-200c target, we investigated the effect of miR-200c modulation on RhoE, PTEN, VEGFR, and MMP9 expression levels. Increased miR-200c expression caused a reduction in VEGFR and MMP9 mRNA and protein, suggesting that VEGFR and MMP9 are targets of miR-200c. In addition, reverse-transcription polymerase chain reaction assays showed that RhoE is target gene of miR-200c and LNA-anti-miR-200c suppressed the expression of PTEN. Flow cytometry and 4',6-diamidino-2-phenylindole staining analysis indicated that miR-200c increased the cisplatin-induced apoptosis which may be associated with suppression of RhoE expression in KATOIII cells, also cell-cycle analysis showed the arrest of cell-cycle progression at the G2 phase. These data demonstrated that miR-200c functioned as a suppressor gene in KATOIII cells. Also, miR-200c can be a potential therapeutic approach to overcome chemoresistance during cisplatin chemotherapy.
(© 2019 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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