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Survivin inhibition is critical for Bcl‐2 family inhibitor, ABT‐263 to induce apoptosis in liver cancer cells
Author(s) -
zhao xiangxuan,
Ogunwobi olorunseun,
Nelson David R,
Liu chen
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.563.13
Subject(s) - survivin , apoptosis , cancer research , inhibitor of apoptosis , chemistry , mechanism (biology) , pharmacology , mechanism of action , cancer cell , bcl 2 family , cancer , medicine , programmed cell death , in vitro , biochemistry , philosophy , epistemology
Background current study was to evaluate the effects of a novel Bcl‐2 inhibitor, ABT‐263, on apoptosis in HCC versus normal hepatocytes and to determine its mechanism of action. Results Low doses of ABT‐263 had no effect on HCC cell apoptosis whereas higher doses induced apoptosis as confirmed by chromatin condensation visible with Hoechst staining and protein expression of cleaved caspases as determined with western blotting analysis. 1 μM of the survivin inhibitor, YM‐155, was also ineffective in inducing apoptosis in HCC cells. However, combined treatment of HCC cells with 1 μM YM‐155 and 1 μM ABT‐263 led to significant apoptotic effects. Further, ABT‐263 accentuated the inhibitory effect of YM‐155 on survivin protein expression. Treatment of survivin siRNA transfected cells with low dose ABT‐263, however, induced significant apoptosis greater than that seen with ABT‐263 treatment alone. Conclusions co‐treatment with low dose ABT‐263 and the survivin inhibitor YM‐155 effectively induces apoptosis in liver cancer cells but not normal hepatocytes. The mechanism underlying this effect involves co‐operative downregulation of survivin expression. Our study suggests that combination of ABT‐263 and YM‐155 may be a potentially safe targeted chemotherapeutic alternative in HCC management. this work was supported by the National Institutes of Health grant R01CA133086 to Chen Liu.