Purpose@#
mTORC1 and
mTORC2 inhibition by Ku-0063794 could confer profound anticancer effects against
cancer cells because it eliminates
feedback activation of Akt. Herein, we aimed to determine anticancer effects of
docetaxel and Ku-0063794, individually or in combination, against
breast cancer cells , especially
triple-negative breast cancer (TNBC)
cells . @*Materials and
Methods @#MCF-7
breast cancer and MDA-MB-231 TNBC
cell lines for
in vitro studies and
mouse xenograft model for in vivo studies were used to investigate the effect of
docetaxel , Ku-0063794, or their combination. @*Results@#In the
in vitro experiments, combination
therapy synergistically reduced
cell viability and induced higher apoptotic
cell death in
breast cancer cells than the individual monotherapies (p < 0.05).
Western blot analysis and flow cytometric
analysis showed that the combination
therapy induced higher apoptotic
cell death than the individual monotherapies (p < 0.05). In the in vivo experiment,
docetaxel and Ku-0063794 combination
therapy reduced the
growth of
MDA-MB-231 cells xenografted in the
nude mice better than in the individual monotherapies (p < 0.05).
Immunohistochemistry showed that the combination
therapy induced the highest expression of cleaved
caspase-3 and the lowest expression of Bcl-xL in the
MDA-MB-231 cells xenografted in the
nude mice (p < 0.05).
Western blot analysis and
immunofluorescence , incorporating both
in vitro and in vivo experiments, consistently validated that unlike individual monotherapies,
docetaxel and Ku-0063794 combination
therapy significantly inhibited
epithelial-mesenchymal transition (EMT) and
autophagy (p < 0.05). @*Conclusion@#These data suggest that
docetaxel and Ku-0063794 combination
therapy has higher anticancer activities over individual monotherapies against MDA-MB-231 TNBC
cells through a greater inhibition of
autophagy and EMT.