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Article Open Access

Paclitaxel suppresses proliferation and induces apoptosis through regulation of ROS and the AKT/MAPK signaling pathway in canine mammary gland tumor cells

  • Authors:
    • Xiaoli Ren
    • Bingbing Zhao
    • Hongjian Chang
    • Min Xiao
    • Yuhong Wu
    • Yun Liu
  • View Affiliations / Copyright

    Affiliations: Department of Veterinary Surgery, College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang 150030, P.R. China
    Copyright: © Ren et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 8289-8299
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    Published online on: April 11, 2018
       https://doi.org/10.3892/mmr.2018.8868
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Abstract

Paclitaxel is a diterpenoid compound, derived from the pacific yew (Taxus brevifolia) berry, which exhibits antineoplastic effects against various types of cancer. However, the antitumor effects and the molecular mechanisms of paclitaxel on canine CHMm cells remain to be elucidated. The aim of the present study was to investigate the antitumor effects of paclitaxel on CHMm cells and identify relevant signal transduction pathways modulated by paclitaxel using multiple methods including MTT assay, flow cytometry, acridine orange/ethidium bromide staining, transmission electron microscopy, determination of cellular reactive oxygen species (ROS), superoxide dismutase (SOD) and malondiadehyde (MDA) and western blotting, the data indicated that paclitaxel decreased cell viability, induced G2/M‑phase cell cycle arrest, suppressed the expression of cyclin B1 and induced apoptosis in a dose‑dependent manner. In addition, paclitaxel upregulated the expression of Bax and cytochrome c, but reduced expression of apoptosis regulator Bcl‑2, resulting in activation of caspase‑3, chromatin condensation, karyopyknosis, intracellular vacuolization, increased production of ROS and MDA, and decreased activity of SOD. However, these effects were inhibited when CHMm cells were treated with N‑acetyl‑L‑cysteine. Furthermore, treatment with paclitaxel inhibited the level of of phospho (p)‑RAC‑α serine/threonine‑protein kinase (AKT) and p‑ribosomal protein S6 kinase proteins, and promoted phosphorylation of P38 mitogen‑activated protein kinase (MAPK) and p‑90 kDa ribosomal protein S6 kinase 1 proteins in CHMm cells. It was observed that paclitaxel in combination with pharmacological inhibitors of the P38 and phosphatidylinositol‑4,5‑bisphosphate 3‑kinase (PI3K) signaling pathways (SB203580 and LY294002, respectively) exerted synergistic inhibitory effects on the proliferation of the CHMm cells. The results of the present study demonstrated that paclitaxel inhibited tumor cell proliferation by increasing intrinsic apoptosis through inhibition of the PI3K/AKT signaling pathway and activation of MAPK signaling pathway in CHMm cells.
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Copy and paste a formatted citation
Spandidos Publications style
Ren X, Zhao B, Chang H, Xiao M, Wu Y and Liu Y: Paclitaxel suppresses proliferation and induces apoptosis through regulation of ROS and the AKT/MAPK signaling pathway in canine mammary gland tumor cells. Mol Med Rep 17: 8289-8299, 2018.
APA
Ren, X., Zhao, B., Chang, H., Xiao, M., Wu, Y., & Liu, Y. (2018). Paclitaxel suppresses proliferation and induces apoptosis through regulation of ROS and the AKT/MAPK signaling pathway in canine mammary gland tumor cells. Molecular Medicine Reports, 17, 8289-8299. https://doi.org/10.3892/mmr.2018.8868
MLA
Ren, X., Zhao, B., Chang, H., Xiao, M., Wu, Y., Liu, Y."Paclitaxel suppresses proliferation and induces apoptosis through regulation of ROS and the AKT/MAPK signaling pathway in canine mammary gland tumor cells". Molecular Medicine Reports 17.6 (2018): 8289-8299.
Chicago
Ren, X., Zhao, B., Chang, H., Xiao, M., Wu, Y., Liu, Y."Paclitaxel suppresses proliferation and induces apoptosis through regulation of ROS and the AKT/MAPK signaling pathway in canine mammary gland tumor cells". Molecular Medicine Reports 17, no. 6 (2018): 8289-8299. https://doi.org/10.3892/mmr.2018.8868
Copy and paste a formatted citation
x
Spandidos Publications style
Ren X, Zhao B, Chang H, Xiao M, Wu Y and Liu Y: Paclitaxel suppresses proliferation and induces apoptosis through regulation of ROS and the AKT/MAPK signaling pathway in canine mammary gland tumor cells. Mol Med Rep 17: 8289-8299, 2018.
APA
Ren, X., Zhao, B., Chang, H., Xiao, M., Wu, Y., & Liu, Y. (2018). Paclitaxel suppresses proliferation and induces apoptosis through regulation of ROS and the AKT/MAPK signaling pathway in canine mammary gland tumor cells. Molecular Medicine Reports, 17, 8289-8299. https://doi.org/10.3892/mmr.2018.8868
MLA
Ren, X., Zhao, B., Chang, H., Xiao, M., Wu, Y., Liu, Y."Paclitaxel suppresses proliferation and induces apoptosis through regulation of ROS and the AKT/MAPK signaling pathway in canine mammary gland tumor cells". Molecular Medicine Reports 17.6 (2018): 8289-8299.
Chicago
Ren, X., Zhao, B., Chang, H., Xiao, M., Wu, Y., Liu, Y."Paclitaxel suppresses proliferation and induces apoptosis through regulation of ROS and the AKT/MAPK signaling pathway in canine mammary gland tumor cells". Molecular Medicine Reports 17, no. 6 (2018): 8289-8299. https://doi.org/10.3892/mmr.2018.8868
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