Effects of anti-ABL tyrosine kinase intrabody on the growth of K562 cells in nude mice / 中国医学科学院学报

ABSTRACT

<p><b>OBJECTIVE</b>To study the effects of anti-ABL tyrosine kinase intrabody on the growth of human chronic myelogenous leukemia (CML) cells in nude mice.</p><p><b>METHODS</b>A recombinant retroviral vector MSCV-ibE-IRES-eGFP was constructed to express intracellular single-chain antibody (intrabody) against ABL tyrosine kinase domain in CML cells. K562 cells were transduced with the retrovirus, eGFP+ cells were then selected by fluorescence-activated cell sorting (FACS). The intrabody mRNA expression was determined by reverse transcription (RT)-polymerase chain reaction (PCR). BCR/ABL and c-ABL protein tyrosine kinase (PTK) activity in the cells was examined. Transduced cells and control group K562 cells were transplanted into nude mice respectively and the tumor sizes were dynamically observed.</p><p><b>RESULTS</b>K562-ibE cell was obtained. Expression of the BCR/ABL and c-ABL protein tyrosine kinase activity of harvested K562-ibE cells were markedly inhibited. At 14, 21 and 28 days after cell injection, the tumor volumes of experimental mice were obviously smaller than that of control mice, about one half of the control groups (P < 0.05).</p><p><b>CONCLUSION</b>The growth of K562-ibE cells was significantly inhibited in vivo. It is possible that inhibition of the BCR/ABL protein tyrosine kinase activity by the intrabody blocked BCR/ABL signal transduction pathway, promoted apoptosis and reduced tumorigenicity of K562 cells in vivo.</p>