[Imatinib induces c-kit positive myeloma cells apoptosis].
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.


CONCLUSIONS
Imatinib inhibits KM3 cells proliferation and induces the cells apoptosis by inhibiting c-kit signalling transduction.
Department Hematology of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Juan
J
Li
Bei-Hui
BH
Huang
Ying
Y
Zhao
Shao-Kai
SK
Luo
D017209:Apoptosis / Q000187:drug effects*; D001549:Benzamides; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D000068877:Imatinib Mesylate; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit