Open Access

Rotenone restrains colon cancer cell viability, motility and epithelial‑mesenchymal transition and tumorigenesis in nude mice via the PI3K/AKT pathway

  • Authors:
    • Wenbo Xiao
    • Yongwei Liu
    • Maolin Dai
    • Yu Li
    • Renqun Peng
    • Shuangjiang Yu
    • Hao Liu
  • View Affiliations

  • Published online on: June 10, 2020     https://doi.org/10.3892/ijmm.2020.4637
  • Pages: 700-708
  • Copyright: © Xiao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Rotenone, a natural hydrophobic pesticide, has been reported to display anticancer activity in a variety of cancer cells. However, the mechanism of rotenone on colon cancer (CC) cell migration, invasion and metastasis is still unknown. In the present study, the cytotoxicity of rotenone on CC cells were detected by the Cell Counting Kit‑8 assay and confirmed by clone formation assay. The effects of rotenone on CC cell invasion and migration activity were determined in vitro by Transwell invasion and wound healing assays, respectively. In addition, to reveal whether rotenone affected the epithelial‑mesenchymal‑transition (EMT) process, reverse transcription‑quantitative PCR, western blotting and immunofluorescence assays were used to detect the expression of EMT markers. The expression levels of the key markers of the PI3K/AKT pathway after rotenone treatment alone or in combination with a PI3K/AKT signaling activator in CC were also detected by western blotting. Finally, the in vivo antitumor effects of rotenone were evaluated in a subcutaneous xenotransplant tumor model treated with an intraperitoneal injection of rotenone. The results of the present study demonstrated that rotenone treatment induced CC cell cytotoxicity and greater effects were observed with increasing concentrations and inhibited cell proliferation compared with untreated cells. In vitro cell function assays revealed that rotenone inhibited CC cell migration, invasion and EMT compared with untreated cells. Mechanically, the phosphorylation levels of AKT and mTOR were downregulated in rotenone‑treated CC cells compared with untreated cells. Additionally, AKT and mTOR phosphorylation levels were increased by the PI3K/AKT signaling activator insulin‑like growth factor 1 (IGF‑1), which was reversed by rotenone treatment. The cell function assays confirmed that the IGF‑1‑activated cell proliferation, migration and invasion were decreased by rotenone treatment. These results indicated that rotenone affected CC cell proliferation and metastatic capabilities by inhibiting the PI3K/AKT/mTOR signaling pathway. In addition, rotenone inhibited tumor growth and metastatic capability of CC, which was confirmed in a xenograft mouse model. In conclusion, the present study revealed that rotenone inhibited CC cell viability, motility, EMT and metastasis in vitro and in vivo by inhibiting the PI3K/AKT/mTOR signaling pathway.
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August-2020
Volume 46 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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APA
Xiao, W., Liu, Y., Dai, M., Li, Y., Peng, R., Yu, S., & Liu, H. (2020). Rotenone restrains colon cancer cell viability, motility and epithelial‑mesenchymal transition and tumorigenesis in nude mice via the PI3K/AKT pathway. International Journal of Molecular Medicine, 46, 700-708. https://doi.org/10.3892/ijmm.2020.4637
MLA
Xiao, W., Liu, Y., Dai, M., Li, Y., Peng, R., Yu, S., Liu, H."Rotenone restrains colon cancer cell viability, motility and epithelial‑mesenchymal transition and tumorigenesis in nude mice via the PI3K/AKT pathway". International Journal of Molecular Medicine 46.2 (2020): 700-708.
Chicago
Xiao, W., Liu, Y., Dai, M., Li, Y., Peng, R., Yu, S., Liu, H."Rotenone restrains colon cancer cell viability, motility and epithelial‑mesenchymal transition and tumorigenesis in nude mice via the PI3K/AKT pathway". International Journal of Molecular Medicine 46, no. 2 (2020): 700-708. https://doi.org/10.3892/ijmm.2020.4637