Oxymatrine reverses 5‑fluorouracil resistance by inhibition of colon cancer cell epithelial‑mesenchymal transition and NF‑κB signaling in vitro

  • Authors:
    • Li Liang
    • Jun Wu
    • Jie Luo
    • Li Wang
    • Zu Xuan Chen
    • Cheng Long Han
    • Ting Qing Gan
    • Jie An Huang
    • Zheng Wen Cai
  • View Affiliations

  • Published online on: November 13, 2019     https://doi.org/10.3892/ol.2019.11090
  • Pages: 519-526
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Abstract

The present study investigated the sensitization of 5‑fluorouracil (5‑FU)‑resistant colon cancer cells in vitro, using oxymatrine, a Chinese herb, and a quinolizidine alkaloid compound extracted from the root of Sophora flavescens. The HCT‑8 colon cancer cell line and its 5‑FU‑resistant subline HCT‑8/5‑FU were treated with 5‑FU and oxymatrine, alone or in combination, at various doses. The cells were subsequently assessed for changes in cell viability, apoptosis and morphology and analyzed by fluorescence microscopy and western blotting. The data demonstrated that HCT‑8/5‑FU markedly increased the dose of 5‑FU required for the suppression of tumor cell viability (78.77±1.90 µg/ml vs. 9.20±0.96 µg/ml in parental HCT‑8 cells), whereas HCT‑8/5‑FU induced the tumor cell epithelial‑mesenchymal transition (EMT). By contrast, oxymatrine alone and in combination with 5‑FU altered HCT‑8/5‑FU cell morphology, apoptosis and EMT phenotypes. The combination of oxymatrine and 5‑FU reduced the protein expression of snail family transcriptional repressor 2 and vimentin, phosphorylated p65 and induced the expression of E‑cadherin, by inhibiting the nuclear factor κB (NF‑κB) signaling pathway. In conclusion, the data from the present study demonstrated that EMT was associated with 5‑FU chemoresistance in HCT‑8/5‑FU colon cancer cells, and that oxymatrine treatment was able to reverse such resistance. Oxymatrine may regulate tumor cell EMT and inactivate the NF‑κB signaling pathway, and may therefore serve as a potential therapeutic drug to reverse 5‑FU resistance in colon cancer cells.
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January-2020
Volume 19 Issue 1

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Liang L, Wu J, Luo J, Wang L, Chen ZX, Han CL, Gan TQ, Huang JA and Cai ZW: Oxymatrine reverses 5‑fluorouracil resistance by inhibition of colon cancer cell epithelial‑mesenchymal transition and NF‑κB signaling in vitro. Oncol Lett 19: 519-526, 2020
APA
Liang, L., Wu, J., Luo, J., Wang, L., Chen, Z.X., Han, C.L. ... Cai, Z.W. (2020). Oxymatrine reverses 5‑fluorouracil resistance by inhibition of colon cancer cell epithelial‑mesenchymal transition and NF‑κB signaling in vitro. Oncology Letters, 19, 519-526. https://doi.org/10.3892/ol.2019.11090
MLA
Liang, L., Wu, J., Luo, J., Wang, L., Chen, Z. X., Han, C. L., Gan, T. Q., Huang, J. A., Cai, Z. W."Oxymatrine reverses 5‑fluorouracil resistance by inhibition of colon cancer cell epithelial‑mesenchymal transition and NF‑κB signaling in vitro". Oncology Letters 19.1 (2020): 519-526.
Chicago
Liang, L., Wu, J., Luo, J., Wang, L., Chen, Z. X., Han, C. L., Gan, T. Q., Huang, J. A., Cai, Z. W."Oxymatrine reverses 5‑fluorouracil resistance by inhibition of colon cancer cell epithelial‑mesenchymal transition and NF‑κB signaling in vitro". Oncology Letters 19, no. 1 (2020): 519-526. https://doi.org/10.3892/ol.2019.11090