Open Access

Tankyrase 1 inhibitior XAV939 increases chemosensitivity in colon cancer cell lines via inhibition of the Wnt signaling pathway

  • Authors:
    • Xuefang Wu
    • Feng Luo
    • Jinbang Li
    • Xueyun Zhong
    • Kunping Liu
  • View Affiliations

  • Published online on: January 26, 2016     https://doi.org/10.3892/ijo.2016.3360
  • Pages: 1333-1340
  • Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Aberrant Wnt signaling pathway is associated with a wide array of tumor types and plays an important role in the drug resistance of cancer stem cells (CSCs). To explore the effects and mechanism of WNT signaling pathway inhibitor XAV939 on drug resistance in colon cancer cells, the colon cancer cells SW480 and SW620 were treated with 5-fluorouracil (5-FU)/cisplatin (DDP) alone or combined with XAV939. Cell cycle distribution, apoptosis level and the percentage of CD133+ cells were detected by flow cytometry. The protein expression of Axin, β-catenin, EpCAM, TERT and DCAMKL-1 was detected by western blotting. XAV939 upregulated Axin , decreased the total and nuclei of β-catenin in SW480 and SW620 cells. Furthermore, XAV939 significantly downregulated the CSC markers EpCAM, TERT and DCAMKL-1 in SW480 cells, as well as EpCAM in SW620 cells. No significant difference was found in the apoptosis of SW480 and SW620 cells with XAV939 treatment, but XAV939 significantly increased apoptosis induced by 5-FU/DDP in SW480 cells, whereas, the effects were slight in SW620 cells. Collectively, we show for the first time that the WNT signaling pathway inhibitor XAV939 was able to significantly increase the apoptosis induced by 5-FU/DDP, accompanied by the protein expression level alternation of β-catenin, Axin and CSC markers in colon cancer cells. Axin, an important component of Wnt/β-catenin signaling pathway could be a potential molecular target for reversing multidrug resistance in colon cancer.

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April 2016
Volume 48 Issue 4

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Copy and paste a formatted citation
APA
Wu, X., Luo, F., Li, J., Zhong, X., & Liu, K. (2016). Tankyrase 1 inhibitior XAV939 increases chemosensitivity in colon cancer cell lines via inhibition of the Wnt signaling pathway. International Journal of Oncology, 48, 1333-1340. https://doi.org/10.3892/ijo.2016.3360
MLA
Wu, X., Luo, F., Li, J., Zhong, X., Liu, K."Tankyrase 1 inhibitior XAV939 increases chemosensitivity in colon cancer cell lines via inhibition of the Wnt signaling pathway". International Journal of Oncology 48.4 (2016): 1333-1340.
Chicago
Wu, X., Luo, F., Li, J., Zhong, X., Liu, K."Tankyrase 1 inhibitior XAV939 increases chemosensitivity in colon cancer cell lines via inhibition of the Wnt signaling pathway". International Journal of Oncology 48, no. 4 (2016): 1333-1340. https://doi.org/10.3892/ijo.2016.3360