Paeonol inhibits proliferation and induces cell apoptosis of human T24 and 5637 bladder cancer cells in vitro and in vivo

Clin Transl Oncol. 2021 Mar;23(3):601-611. doi: 10.1007/s12094-020-02455-y. Epub 2020 Jul 20.

Abstract

Purpose: Paeonol is a natural chemical medicine derived from the bark of peony root, which has been found to inhibit tumor activity in various tumor cell lines, and can play a synergistic anti-tumor effect with chemotherapy or radiotherapy.

Methods: We used paeonol to act on human bladder cancer T24 and 5637 cells, and established xenograft tumor in nude mice by subcutaneous injection of T24 cells.

Results: CCK-8 assay and plate cloning experiments showed that paeonol could inhibit the proliferation of T24 and 5637 cells in vitro. The results of flow cytometry and the detection of BAX, Bcl-2 and Caspase-3 proteins suggested that paeonol can induce apoptosis of T24 and 5637 cells in vitro. Tumor formation, TUNEL detection and immunohistochemical results of Ki67, BAX, Bcl-2 and Caspase-3 in nude mice showed that paeonol could inhibit T24 cell proliferation and induce apoptosis in vivo, thus inhibiting tumor growth. Further research revealed that paeonol could reduce phosphorylation expression of PI3K and AKT in T24 and 5637 cells.

Conclusion: We confirmed that paeonol could inhibit proliferation and induce apoptosis of human bladder cancer T24 and 5637 cells in vitro and in vivo, inhibit the growth of T24 tumor-forming nude mice, and possibly play a role by inhibiting the PI3K/AKT signaling pathway, so as to provide a potential therapeutic drug for bladder cancer.

Keywords: Bladder cancer; Cell apoptosis; Cell proliferation; Paeonol.

MeSH terms

  • Acetophenones / pharmacology*
  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Caspase 3 / analysis
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Flow Cytometry
  • Humans
  • In Situ Nick-End Labeling
  • In Vitro Techniques
  • Ki-67 Antigen / analysis
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Urinary Bladder Neoplasms / chemistry
  • Urinary Bladder Neoplasms / drug therapy
  • Urinary Bladder Neoplasms / pathology*
  • Xenograft Model Antitumor Assays
  • bcl-2-Associated X Protein / analysis

Substances

  • Acetophenones
  • Antineoplastic Agents, Phytogenic
  • BCL2 protein, human
  • Ki-67 Antigen
  • MKI67 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • paeonol
  • Proto-Oncogene Proteins c-akt
  • CASP3 protein, human
  • Caspase 3