A combination of STI571 and BCR-ABL1 siRNA with overexpressed p15INK4B induced enhanced proliferation inhibition and apoptosis in chronic myeloid leukemia
p15INK4B, a cyclin-dependent kinase inhibitor, has been recognized as a tumor suppressor. Loss of or methylation of the p15INK4B gene in chronic myeloid leukemia (CML) cells enhances myeloid progenitor formation from common myeloid progenitors. Therefore, we examined the effects of overexpressed p15...
| Main Authors: | , , , , , |
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| Format: | Online |
| Language: | English |
| Published: |
Associação Brasileira de Divulgação Científica
2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4244677/ |
| Summary: | p15INK4B, a cyclin-dependent kinase inhibitor, has been recognized as a tumor
suppressor. Loss of or methylation of the p15INK4B gene in chronic
myeloid leukemia (CML) cells enhances myeloid progenitor formation from common
myeloid progenitors. Therefore, we examined the effects of overexpressed p15INK4B on
proliferation and apoptosis of CML cells. Overexpression of p15INK4B inhibited the
growth of K562 cells by downregulation of cyclin-dependent kinase 4 (CDK4) and cyclin
D1 expression. Overexpression of p15INK4B also induced apoptosis of K562 cells by
upregulating Bax expression and downregulating Bcl-2 expression. Overexpression of
p15INK4B together with STI571 (imatinib) or BCR-ABL1 small interfering RNA (siRNA)
also enhanced growth inhibition and apoptosis induction of K562 cells. The enhanced
effect was also mediated by reduction of cyclin D1 and CDK4 and regulation of Bax and
Bcl-2. In conclusion, our study may provide new insights into the role of p15INK4B in
CML and a potential therapeutic target for overcoming tyrosine kinase inhibitor
resistance in CML. |
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