Abstract | OBJECTIVE: STUDY DESIGN: The expression and functional role of Stat3 and survivin was evaluated in 2 salivary gland adenocarcinoma cell lines (HSY and HSG). In addition, the effects of the NSAID sulindac and other cyclooxygenase (COX) inhibitors on Stat3 and survivin expression and on cell proliferation and apoptosis of HSY and HSG cells were analyzed. RESULTS:
Messenger RNA and protein expression of Stat3 and survivin was detected in HSY and HSG cell lines. Treatment of these cells with siRNA against Stat3 or survivin inhibited cell proliferation and induced apoptosis. Moreover, Stat3 siRNA treatment down-regulated the protein and mRNA expression of survivin, and survivin forced expression partially reversed the antineoplastic effects of Stat3 siRNA treatment. Treatment of HSY and HSG cells with the NSAID sulindac, but not other COX inhibitors, induced significant decreases in cell proliferation and increases in apoptosis, accompanied by down-regulation of Stat3 and survivin expression. In contrast, survivin forced expression or transfection with constitutively active Stat3 attenuated the effects of sulindac on cell growth and apoptosis. CONCLUSIONS: Taken together, these data support the importance of the constitutive Stat3 signaling for growth and survival of salivary gland cancer cells through the induction of survivin. Inhibition of the oncogenic Stat3-survivin pathway in these cells can be achieved by selective targeting techniques or treatment with the NSAID sulindac and holds promise for the treatment of salivary gland cancer.
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Authors | Nikolaos G Nikitakis, Mark A Scheper, Vasileios S Papanikolaou, John J Sauk |
Journal | Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics
(Oral Surg Oral Med Oral Pathol Oral Radiol Endod)
Vol. 107
Issue 6
Pg. 826-36
(Jun 2009)
ISSN: 1528-395X [Electronic] United States |
PMID | 19272804
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Retracted Publication)
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Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Antineoplastic Agents
- BIRC5 protein, human
- Cyclooxygenase Inhibitors
- Inhibitor of Apoptosis Proteins
- Microtubule-Associated Proteins
- RNA, Messenger
- STAT3 Transcription Factor
- Survivin
- Sulindac
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Topics |
- Adenocarcinoma
(drug therapy, metabolism)
- Anti-Inflammatory Agents, Non-Steroidal
(pharmacology)
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects, physiology)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cyclooxygenase Inhibitors
(pharmacology)
- Gene Expression Regulation, Neoplastic
(drug effects, physiology)
- Humans
- Inhibitor of Apoptosis Proteins
- Microtubule-Associated Proteins
(drug effects, genetics, metabolism)
- RNA, Messenger
(analysis)
- STAT3 Transcription Factor
(drug effects, genetics, metabolism)
- Salivary Gland Neoplasms
(drug therapy, metabolism)
- Signal Transduction
(drug effects, physiology)
- Sulindac
(pharmacology)
- Survivin
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