GSK-3β inhibitor 6-bromo-indirubin-3'-oxime promotes both adhesive activity and drug resistance in colorectal cancer cells

  • Authors:
    • Kunping Liu
    • Jinbang Li
    • Xuefang Wu
    • Meixiang Chen
    • Feng Luo
    • Jun Li
  • View Affiliations

  • Published online on: October 16, 2017     https://doi.org/10.3892/ijo.2017.4163
  • Pages:1821-1830
0

Abstract

Multi-targets inhibitor 6-bromo-indirubin-3'-oxime (BIO) has diverse biological effects on cancer cells. The key component of the β-catenin destruction complex glycogen synthase kinase 3β (GSK-3β), one of the major target for BIO, polyubiquitination and degradation of the main oncoprotein β-catenin in colorectal cancer (CRC). In the present study, we evaluated the effect of BIO on drug resistance and biological properties of CRC cells. Whole-genome transcriptional profiling revealed that differentially expressed genes were mainly centered on well-characterized signaling pathways including stem cell, cell adhesion and cell growth in BIO-treated CRC cells. BIO treatment downregulated migration and invasion abilities of CRC cells, accompanying with MMP-9 downregulated and E-cadherin upregulated CRC cells. BIO treatment decreased apoptosis induced by 5-Fu/DDP in CRC SW480 cells. In addition, BIO treatment reversed the 5-Fu-induced CD133+ cell downregulation trend in CRC SW620 cells. After incubation with BIO, the expression levels of EpCAM, TERT and DCAMKL-1 proteins were upregulated in CRC cells. BIO treatment downregulated the activity of GSK-3β, upregulated and transported β-catenin to the nucleus in CRC cells. Our findings reveal that BIO treatment upregulated stemness, adhesive and chemoresistance of CRC cells. GSK-3β inhibition and WNT/β-catenin activation by BIO, may partly result in the biological behavior alterations in CRC cells.

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December 2017
Volume 51 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

2016 Impact Factor: 3.079
Ranked #33/217 Oncology
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Copy and paste a formatted citation
APA
Liu, K., Li, J., Wu, X., Chen, M., Luo, F., & Li, J. (2017). GSK-3β inhibitor 6-bromo-indirubin-3'-oxime promotes both adhesive activity and drug resistance in colorectal cancer cells. International Journal of Oncology, 51, 1821-1830. https://doi.org/10.3892/ijo.2017.4163
MLA
Liu, K., Li, J., Wu, X., Chen, M., Luo, F., Li, J."GSK-3β inhibitor 6-bromo-indirubin-3'-oxime promotes both adhesive activity and drug resistance in colorectal cancer cells". International Journal of Oncology 51.6 (2017): 1821-1830.
Chicago
Liu, K., Li, J., Wu, X., Chen, M., Luo, F., Li, J."GSK-3β inhibitor 6-bromo-indirubin-3'-oxime promotes both adhesive activity and drug resistance in colorectal cancer cells". International Journal of Oncology 51, no. 6 (2017): 1821-1830. https://doi.org/10.3892/ijo.2017.4163