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Investigating the Protective Effects of Platycodin D on Non-Alcoholic Fatty Liver Disease in a Palmitic Acid-Induced In Vitro Model
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[Inhibitory effect and mechanism of platycodin D combined with imatinib on K562/R]

Qun Dai1, Yu-Qing Ge1

  • 1First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China.

Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica
|March 20, 2018
PubMed

Insights

Platycodin D enhances imatinib sensitivity in resistant leukemia cells. Combining Platycodin D with imatinib significantly inhibits proliferation and induces apoptosis by targeting key proteins and signaling pathways.

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Oncology

Background:

  • Platycodin D (PD) shows promise against various cancers, including leukemia.
  • Imatinib (IM) is a standard treatment for chronic myeloid leukemia (CML), but resistance is a challenge.
  • The mechanism by which PD affects imatinib-resistant cells remains largely unknown.

Purpose of the Study:

  • To investigate the efficacy of Platycodin D, alone or combined with imatinib, against imatinib-resistant K562/R leukemia cells.
  • To elucidate the molecular mechanisms underlying the combined treatment's effects on drug-resistant CML cells.

Main Methods:

  • Cell proliferation was assessed using the CCK8 assay.
  • Apoptosis was detected via Annexin V-FITC/PI double staining.
  • Western blotting was employed to analyze protein expression levels of key apoptotic and signaling molecules (cleaved caspase-3, cleaved caspase-9, PARP, Bcr/abl, p-AKT, p-mTOR).

Main Results:

  • The combination of PD and imatinib demonstrated a significantly greater inhibitory effect on K562/R cell proliferation and apoptosis compared to single-agent treatments.
  • Combined therapy led to increased expression of cleaved caspase-3, cleaved caspase-9, and cleaved PARP.
  • PD and imatinib combination downregulated PARP, Bcr/abl, p-AKT, and p-mTOR protein levels.

Conclusions:

  • Platycodin D effectively resensitizes imatinib-resistant leukemia cells to imatinib.
  • The combination therapy shows superior efficacy in inhibiting proliferation and inducing apoptosis.
  • The observed effects are mediated through the modulation of Bcr/abl protein expression and the PI3K/AKT/mTOR signaling pathway.
Keywords:
Bcr/abl fusion geneK562/RPI3K/AKT/mTOR signal pathwayimatinibplatycodin D

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