[STI571 induces apoptosis of K562 cells through down-regulation of anti-apoptotic protein Mcl-1 and Bcl-xl expression].
This study was aimed to investigate the effect of STI571, an inhibitor of tyrosine kinase, on the proliferation and apoptosis of chronic myelogenous leukemia (CML) cells as well as expression of anti-apoptotic protein Mcl-1, and to explore the possible role of Mcl-1 in apoptosis-inducing mechanism. K562 cell line was used to observe the effect of STI571 on CML cells. Proliferation and cytotoxicity were analyzed by MTT assay. The apoptotic cells were labelled with Annexin V-FITC and PI and then analyzed by flow cytometry. The expression of apoptotic-related proteins in K562 cells was determined by Western blot with specific antibodies. The results showed that STI571 significantly inhibited the proliferation and induced apoptosis of K562 cells in a dose-and time-dependent manner. Coincidently, the protein phosphorylation on tyrosine residues was reduced and the expressions of anti-apoptotic protein Mcl-1 and Bcl-xl were down-regulated after exposure to STI571. It is concluded that STI571 induces the apoptosis of CML cells by down-regulating the expressions of Mcl-1 and Bcl-xl, which suggests that Mcl-1 and Bcl-xl may play an important role in anti-apoptotic process of CML cells.
Zhang
Bao-Zhen
BZ
Department of Hematology, Peking University First Hospital, Beijing 100034, China.
Ren
Han-Yun
HY
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001549:Benzamides; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000068877:Imatinib Mesylate; D020014:K562 Cells; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology*; D051020:bcl-X Protein / Q000378:metabolism*
D000970:Antineoplastic Agents; C494811:BCL2L1 protein, human; D001549:Benzamides; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D010879:Piperazines; D019253:Proto-Oncogene Proteins c-bcl-2; D011743:Pyrimidines; D051020:bcl-X Protein; D000068877:Imatinib Mesylate