Survivin downregulation by siRNA sensitizes human hepatoma cells to TRAIL-induced apoptosis.

Abstract:

:Survivin, an anti-apoptotic protein, is abundantly expressed in a variety of cancer cells, including hepatoma cells, resulting in the resistance of these cells to various apoptotic stimuli. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is known to induce cancer cell-specific apoptosis, but hepatoma cells are resistant to TRAIL-induced apoptosis. In the present study, we have examined whether the downregulation of survivin by short interfering RNA (siRNA) promotes spontaneous or TRAIL-induced apoptosis in Huh-7 human hepatoma cells. Survivin siRNA transfection downregulated the expression of survivin in Huh-7 cells and reduced cell viability by 20% through inducing spontaneous apoptosis. TRAIL (1 to 2 ng/ml) only slightly induced apoptosis in Huh-7 cells; however, survivin siRNA transfection apparently enhanced TRAIL-induced apoptosis. These results suggest that the level of survivin is linked to the susceptibility of Huh-7 cells to TRAIL. It is possible that survivin downregulation by siRNA combined with TRAIL administration may provide a new therapeutic strategy against hepatoma.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Nakao K,Hamasaki K,Ichikawa T,Arima K,Eguchi K,Ishii N

subject

Has Abstract

pub_date

2006-08-01 00:00:00

pages

389-92

issue

2

eissn

1021-335X

issn

1791-2431

journal_volume

16

pub_type

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