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Published on: January 7, 2019
[Imatinib induces c-kit positive myeloma cells apoptosis]
Juan Li1, Bei-Hui Huang, Ying Zhao
1Department Hematology of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Objective:
To explore the influence of Imatinib on multiple myeloma cells expressing c-kit in vitro and its mechanism.
Methods:
KM3 cells were treated with Imatinib at different concentrations, and cell growth index were evaluated by XTT assay, cell cycle by flow cytometry, apoptosis by Annexin V/ PI and DNA ladder, and change in protein level by Western blot.
Results:
Imatinib inhibited proliferation of KM3 cells at concentrations more than 0.25 micromol/L in a dose-dependent manner, and the 48 h IC50 was 0.33 micromol/L (P < 0.01). Imatinib arrested cell in C0/G1 phase. Annexin V/PI staining and DNA ladder indicated that Imatinib had a substantial effect on inducing apoptosis of KM3 cells in a dose-dependent manner and induced pro-caspase-3 and poly ADP-ribose polymerase (PARP) cleaved. Imatinib inhibited expression of c-kit and provoked a decrease of IL-6 induced c-kit phosphorylation in vitro.
Conclusion:
Imatinib inhibits KM3 cells proliferation and induces the cells apoptosis by inhibiting c-kit signalling transduction.
Insights
Imatinib effectively inhibits multiple myeloma cell proliferation and induces apoptosis by targeting c-kit signaling. This study demonstrates Imatinib
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Context:
- Multiple myeloma is a cancer of plasma cells.
- c-kit is a receptor tyrosine kinase implicated in various cancers.
- Imatinib is a tyrosine kinase inhibitor.
Purpose:
- To investigate the in vitro effects of Imatinib on multiple myeloma cells expressing c-kit.
- To elucidate the underlying mechanisms of Imatinib's action.
Summary:
- Imatinib demonstrated dose-dependent inhibition of KM3 multiple myeloma cell proliferation with an IC50 of 0.33 micromol/L.
- Imatinib induced G0/G1 cell cycle arrest and apoptosis, evidenced by Annexin V/PI staining and DNA ladder assays.
- The drug reduced c-kit expression and inhibited IL-6-induced c-kit phosphorylation, suggesting c-kit signaling pathway inhibition.
Impact:
- Imatinib exhibits therapeutic potential against c-kit expressing multiple myeloma.
- The findings provide mechanistic insights into Imatinib's anti-myeloma activity.
- This research may inform the development of targeted therapies for multiple myeloma.
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