Tangeretin enhances radiosensitivity and inhibits the radiation-induced epithelial-mesenchymal transition of gastric cancer cells

  • Authors:
    • Xukui Zhang
    • Luming Zheng
    • Yinggang Sun
    • Tianxiao Wang
    • Baocheng Wang
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  • Published online on: May 15, 2015     https://doi.org/10.3892/or.2015.3982
  • Pages: 302-310
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Abstract

Irradiation has been reported to increase radioresistance and epithelial-mesenchymal transition (EMT) in gastric cancer (GC) cells. The Notch pathway is critically implicated in cancer EMT and radioresistance. In the present study, we investigated the use of a Notch-1 inhibiting compound as a novel therapeutic candidate to regulate radiation-induced EMT in GC cells. According to previous screening, tangeretin, a polymethoxylated flavonoid from citrus fruits was selected as a Notch-1 inhibitor. Tangeretin enhanced the radiosensitivity of GC cells as demonstrated by MTT and colony formation assays. Tangeretin also attenuated radiation-induced EMT, invasion and migration in GC cells, accompanied by a decrease in Notch-1, Jagged1/2, Hey-1 and Hes-1 expressions. Tangeretin triggered the upregulation of miR-410, a tumor-suppressive microRNA. Furthermore, re-expression of miR-410 prevented radiation-induced EMT and cell invasion. An in vivo tumor xenograft model confirmed the antimetastasis effect of tangeretin as we observed in vitro. In nude mice, tumor size was considerably diminished by radiation plus tangeretin co-treatment. Tangeretin almost completely inhibited lung metastasis induced by irradiation. Tangeretin may be a novel antimetastatic agent for radiotherapy.
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July-2015
Volume 34 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Zhang X, Zheng L, Sun Y, Wang T and Wang B: Tangeretin enhances radiosensitivity and inhibits the radiation-induced epithelial-mesenchymal transition of gastric cancer cells. Oncol Rep 34: 302-310, 2015.
APA
Zhang, X., Zheng, L., Sun, Y., Wang, T., & Wang, B. (2015). Tangeretin enhances radiosensitivity and inhibits the radiation-induced epithelial-mesenchymal transition of gastric cancer cells. Oncology Reports, 34, 302-310. https://doi.org/10.3892/or.2015.3982
MLA
Zhang, X., Zheng, L., Sun, Y., Wang, T., Wang, B."Tangeretin enhances radiosensitivity and inhibits the radiation-induced epithelial-mesenchymal transition of gastric cancer cells". Oncology Reports 34.1 (2015): 302-310.
Chicago
Zhang, X., Zheng, L., Sun, Y., Wang, T., Wang, B."Tangeretin enhances radiosensitivity and inhibits the radiation-induced epithelial-mesenchymal transition of gastric cancer cells". Oncology Reports 34, no. 1 (2015): 302-310. https://doi.org/10.3892/or.2015.3982