LLL-3, a STAT3 inhibitor, represses BCR-ABL-positive cell proliferation, activates apoptosis and improves the effects of Imatinib mesylate
The chimeric protein BCR-ABL, a constitutively active protein-tyrosine kinase, triggers downstream signalling proteins, such as STAT3, ultimately resulting in the survival of myeloid progenitors in BCR-ABL-positive leukemias. Here, we evaluated the effect of LLL-3, an inhibitor of STAT3 activity, on cell viability and its addictive effects with Imatinib mesylate (IM) treatment in BCR-ABL-positive cells.
Viability of cell lines was determined using the WST-1 assay in response to drug treatment, either LLL-3 alone or in conjunction with IM. Annexin V-FITC/PI staining, sub-G1 DNA content and Caspase-3/7 activation assays were performed to evaluate apoptosis.
LLL-3 treatment decreased cell viability, triggered apoptosis and activated Caspases-3/7 in K562 cells. LLL-3 increases IM treatment to inhibited cell viability and activation of apoptosis in BCR-ABL-positive cell lines.
LLL-3 reduced cell viability and induced apoptosis in K562 cells. Moreover, the observed addictive effects of co-treatment with IM and LLL-3 suggest this combination has therapeutic potential.
KeywordsLLL-3 STAT3 BCR-ABL Imatinib
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