miR-200c induces resistance to doxorubicin through the Wnt/beta-catenin signaling pathway in bladder cancer cells

doi:10.12092/j.issn.1009-2501.2018.05.005

Abstract

Abstract:

AIM: To investigate the relationship between miR-200c expression and the response to DOX in bladder cancer cells. METHODS: Changes in the growthinhibitory effect of DOX on bladder cancer cells (RT4,RT112,T24 and TCCSUP) were examined after overexpression or suppression of miR-200c.The effect of miR-200c on the Wnt/beta-catenin signaling pathway were also examined to investigate whether the altered growth-inhibitory effect by miR-200c suppression was weakened after the addition of Wnt3a,a Wnt/beta-catenin signaling activator. RESULTS: RT4 and T24 cells transfected with anti-miR-200c showed significantly lower resistance to DOX. In the anti-miR-200c-transfected cells, DOX induced significantly larger numbers of apoptotic cells and S phase accumulation compared to control cells, demonstrated by Annexin V assay and flow cytometric analysis of the cell cycle, respectively. The transfected cells showed overexpression of putative target molecules including Dkk1, Kremen2 and sFRP2 and lower activation of the Wnt/beta-catenin signaling pathway.The addition of Wnt3a weakened the augmented growth-inhibitory effect of anti-miR-200c transfection. CONCLUSION: miR-200c expression correlates significantly with the growth-inhibitory effect of DOX and that activation of the Wnt/beta-catenin signaling pathway mediates the miR-200c-induced resistance to DOX in bladder cancer cell lines.

Key words: bladder cancer, doxorubicin, microRNA, miR-200c, Wnt/beta-catenin signaling pathway

CLC Number:

R965.2

LIU lei, LI Yixiao, WAN Bo, ZENG Qing. miR-200c induces resistance to doxorubicin through the Wnt/beta-catenin signaling pathway in bladder cancer cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(5): 510-516.

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