Silencing of the integrin-linked kinase gene induces the apoptosis in ovarian carcinoma.

Abstract

CONTEXT:

Integrin-linked kinase (ILK), a multidomain focal adhesion protein serine/threonine kinase, plays an essential role in ovarian carcinoma. There are reports that the expression and activity of ILK are increased in ovarian cancer.

OBJECTIVE:

To test the hypothesis that ILK pathway mediates the apoptosis of ovarian carcinoma SKOV3 cell influencing the cell survival, we performed these studies.

MATERIALS AND METHODS:

We applied lentivirus transfection, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT), apoptotic proteins expressions assay, and Hoechst to study our hypothesis.

RESULTS:

We found that silencing of the ILK increases the cell cytotoxic, growth inhibition, and apoptosis. Moreover, after blocking the activation of ILK with ILK shRNA, up-regulation of pro-apoptotic bax expression and down-regulation of the anti-apoptotic bcl-2 expression were found in ovarian cancer SKOV3 cell line. These were associated with an increasing cleaved caspase-3 activity and chromatin condensation of cell nuclear. Furthermore, the expressions of fas and fas ligand (fasL), belonging to the tumor necrosis factor family and controlling the cell apoptosis, were also enhanced.

CONCLUSIONS:

Thus, these findings indicate that both the intrinsic pathway and the extrinsic death receptor pathway are involved in the process that silencing of the ILK gene induces the apoptosis in ovarian carcinoma SKOV3 cell.

• Authors: Qian Liu, Lei Xiao, Dandan Yuan, Xiaoding Shi, Peiling Li
• Journal: Journal of receptor and signal transduction research (J Recept Signal Transduct Res) Vol. 32 Issue 2 Pg. 120-7 (Apr 2012) ISSN: 1532-4281 [Electronic] England
• PMID: 22384810 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BAX protein, human
• FAS protein, human
• FASLG protein, human
• Fas Ligand Protein
• Proto-Oncogene Proteins c-bcl-2
• RNA, Messenger
• RNA, Small Interfering
• bcl-2-Associated X Protein
• fas Receptor
• integrin-linked kinase
• Protein Serine-Threonine Kinases
• Caspase 3

Topics

• Apoptosis
• Blotting, Western
• Caspase 3 (genetics, metabolism)
• Cell Proliferation
• Fas Ligand Protein (genetics, metabolism)
• Female
• Flow Cytometry
• Humans
• Ovarian Neoplasms (genetics, metabolism, pathology)
• Protein Serine-Threonine Kinases (antagonists & inhibitors, genetics, metabolism)
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• RNA, Messenger (genetics)
• RNA, Small Interfering (genetics)
• Real-Time Polymerase Chain Reaction
• Tumor Cells, Cultured
• bcl-2-Associated X Protein (genetics, metabolism)
• fas Receptor (genetics, metabolism)