Background:
Chronic myeloid leukemia (CML), is characterized by a reciprocal translocation t(9;22) and forms the
BCR/ABL1 fusion gene, which is called the Philadelphia chromosome. The therapeutic targets for CML patients which are mediated with
BCR/ABL1 oncogenic are tyrosine kinase inhibitors such as imatinib, dasatinib, and nilotinib. The latter two of which have been approved
for the treatment of imatinib-resistant or intolerance CML patients. Mitotic catastrophe (MC) is one of the non-apoptotic mechanisms
which frequently initiated in types of cancer cells in response to anti-cancer therapies; pharmacological inhibitors of G2 checkpoint
members or genetic suppression of PLK1, PLK2, ATR, ATM, CHK1, and CHK2 can trigger DNA-damage-stimulated mitotic catastrophe.
PLK1, AURKA/B anomalously expressed in CML cells, that phosphorylation and activation of PLK1 occur by AURKB at centromeres
and kinetochores.
Objective:
The purpose of this study was to investigate the effect of dasatinib on the expression of genes in MC and apoptosis pathways
in K562 cells.
Methods:
Total RNA was isolated from K-562 cells treated with the IC50 value of dasatinib and untreated cells as a control group. The
expression of MC and apoptosis-related genes were analyzed by the qRT-PCR system. Results: The array-data demonstrated that
dasatinib-treated K562 cells significantly caused the decrease of several genes (AURKA, AURKB, PLK, CHEK1, MYC, XPC, BCL2, and
XRCC2).
Conclusion:
The evidence supply a basis to support clinical researches for the suppression of oncogenes such as PLKs with AURKs in
the treatment of types of cancer especially chronic myeloid leukemia.
Receptor-mediated endocytosis of transferrin in K562 cells.
