| Anti-proliferative Activity of NVP-BEZ235, a Dual Inhibitor of PI3K
and mTOR, in Colorectal Cancer Cells |
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Deok Bae Park, Youngki Lee |
Correspondence:
Youngki Lee,
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| Abstract |
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In colorectal cancer diverse mutations of genes involved in signal transduction pathways for cell survival and proliferation are
observed, which have been the therapeutic targets for improvement of malignancies. The present study was undertaken to
investigate whether NVP-BEZ235 (BEZ235), a dual inhibitor of PI3K/mTOR, shows any anti-proliferative effect on colorectal cell
lines harboring KRAS, and/or, PIK3CA, and/or BRAF mutations and to determine whether these mutational status affects the
sensitivity of colorectal cancer cells to BEZ235. BEZ235 treatment induced growth inhibition in all four cell lines tested. HCT116
cell line with both KRAS and PIK3CA mutation, and LoVo cell line with KRAS mutation showed higher IC50 values (643±19 nM
and 663±7 nM, respectively) at 3 days post-treatment. On the other hand, HCT15 cell line harboring the same mutational
status as HCT116 with KRAS and PIK3CA mutation, and HT29 cell line with BRAF mutation were more sensitive to BEZ235 (IC50
values; 25±7 nM and 213±40 nM, respectively). At suboptimal concentrations of BEZ235 (50 nM), HCT116 and LoVo cell lines
were less responsive comparing with the HCT15 and HT29 cell lines, whereas a higher doses of BEZ235 showed a similar
response of growth inhibition in all four cell lines tested except HCT15. These studies provide the preclinical rationale for
evaluating the efficacy of BEZ235. |
| Key Words:
NVP-BEZ235, PI3K, MTOR, KRAS, BRAF, colorectal cancer |
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