COX-independent Antineoplastic Effects of Sulindac in Oral Cancer are Mediated by Survivin Down-regulation

Background: Cyclooxygenase (COX) inhibitors are reported to exert anti-proliferative and pro-apoptotic effects on cancer. The effects of COX inhibitors on oral squamous cell carcinoma (SCC) and survivin expression were assessed. Materials and Methods: Primary oral SCC were analyzed immunohistochemic...

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Veröffentlicht in:Anticancer research 2006-11, Vol.26 (6B), p.4103-4113
Hauptverfasser: SCHEPER, Mark A, SAUK, John J, NIKITAKIS, Nikolaos G
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creator SCHEPER, Mark A
SAUK, John J
NIKITAKIS, Nikolaos G
description Background: Cyclooxygenase (COX) inhibitors are reported to exert anti-proliferative and pro-apoptotic effects on cancer. The effects of COX inhibitors on oral squamous cell carcinoma (SCC) and survivin expression were assessed. Materials and Methods: Primary oral SCC were analyzed immunohistochemically, and oral SCC cell lines were assessed using RT-PCR, Western blot, cell proliferation and apoptosis assays, following treatment with various COX inhibitors, SiRNA against survivin, or survivin forced expression. Results: Survivin was expressed in all studied tumors. SiRNA against survivin or treatment with sulindac, but not other COX inhibitors, decreased survivin expression and tumor cell proliferation and increased apoptosis. Forced expression of survivin attenuated sulindac's effects. Conclusion: Survivin is implicated as a marker and treatment target in oral SCC, inhibition of which causes reduction of cell proliferation and induction of apoptosis. Down-regulation of survivin expression by sulindac provides an explanation for its antineoplastic effects.
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The effects of COX inhibitors on oral squamous cell carcinoma (SCC) and survivin expression were assessed. Materials and Methods: Primary oral SCC were analyzed immunohistochemically, and oral SCC cell lines were assessed using RT-PCR, Western blot, cell proliferation and apoptosis assays, following treatment with various COX inhibitors, SiRNA against survivin, or survivin forced expression. Results: Survivin was expressed in all studied tumors. SiRNA against survivin or treatment with sulindac, but not other COX inhibitors, decreased survivin expression and tumor cell proliferation and increased apoptosis. Forced expression of survivin attenuated sulindac's effects. Conclusion: Survivin is implicated as a marker and treatment target in oral SCC, inhibition of which causes reduction of cell proliferation and induction of apoptosis. 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The effects of COX inhibitors on oral squamous cell carcinoma (SCC) and survivin expression were assessed. Materials and Methods: Primary oral SCC were analyzed immunohistochemically, and oral SCC cell lines were assessed using RT-PCR, Western blot, cell proliferation and apoptosis assays, following treatment with various COX inhibitors, SiRNA against survivin, or survivin forced expression. Results: Survivin was expressed in all studied tumors. SiRNA against survivin or treatment with sulindac, but not other COX inhibitors, decreased survivin expression and tumor cell proliferation and increased apoptosis. Forced expression of survivin attenuated sulindac's effects. Conclusion: Survivin is implicated as a marker and treatment target in oral SCC, inhibition of which causes reduction of cell proliferation and induction of apoptosis. 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Stomatology</subject><subject>RNA, Small Interfering</subject><subject>Sulindac - pharmacology</subject><subject>Tumors</subject><subject>Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology</subject><issn>0250-7005</issn><issn>1791-7530</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpF0MtOwzAQBVALgWgp_ALyBnaRHDuxk2UpT6moC0BiF02ScevKeWAnrfr3WKKom_Hm6HrunJFprPI4Uqlg52TKeMoixVg6IVfebxmTMs_EJZnEirM45vGUbBer78i0NfYYRjvQeTuYFrvegh9MRZ-0xmrwtNP0Y7QBQkVNS1cOLF1AW6Gj4JC-Y21gwJqWh-DczuwCeuz2beRwPVoYTNdekwsN1uPN8Z2Rr-enz8VrtFy9vC3my2jDFRsiLus6rKYypSXoSoqMaZQ6wzThqUCdoKq4ikUokKsSE52nLC9TyBMOkColZuT-L7d33c-Ifiga4yu0FkKv0Rcy4yrPQsKM3B7hWDZYF70zDbhD8X-dAO6OAHwFVrtQ2PiTy4RkGZOnHzdmvdkbh4VvwNoQKwpwXBbyoUhiJsQvX1l7ZA</recordid><startdate>20061101</startdate><enddate>20061101</enddate><creator>SCHEPER, Mark A</creator><creator>SAUK, John J</creator><creator>NIKITAKIS, Nikolaos G</creator><general>International Institute of Anticancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20061101</creationdate><title>COX-independent Antineoplastic Effects of Sulindac in Oral Cancer are Mediated by Survivin Down-regulation</title><author>SCHEPER, Mark A ; SAUK, John J ; NIKITAKIS, Nikolaos G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h270t-26dd121787f6afc6380fe6f8e54253ef4e7c271301197be4f9509b5a942aa5773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Apoptosis - drug effects</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Cell Proliferation - drug effects</topic><topic>Cyclooxygenase Inhibitors - pharmacology</topic><topic>DNA Primers</topic><topic>Down-Regulation - drug effects</topic><topic>Humans</topic><topic>Inhibitor of Apoptosis Proteins</topic><topic>Medical sciences</topic><topic>Microtubule-Associated Proteins - antagonists &amp; inhibitors</topic><topic>Microtubule-Associated Proteins - metabolism</topic><topic>Mouth Neoplasms - metabolism</topic><topic>Mouth Neoplasms - pathology</topic><topic>Neoplasm Proteins - antagonists &amp; inhibitors</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Otorhinolaryngology. Stomatology</topic><topic>RNA, Small Interfering</topic><topic>Sulindac - pharmacology</topic><topic>Tumors</topic><topic>Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SCHEPER, Mark A</creatorcontrib><creatorcontrib>SAUK, John J</creatorcontrib><creatorcontrib>NIKITAKIS, Nikolaos G</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Anticancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SCHEPER, Mark A</au><au>SAUK, John J</au><au>NIKITAKIS, Nikolaos G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>COX-independent Antineoplastic Effects of Sulindac in Oral Cancer are Mediated by Survivin Down-regulation</atitle><jtitle>Anticancer research</jtitle><addtitle>Anticancer Res</addtitle><date>2006-11-01</date><risdate>2006</risdate><volume>26</volume><issue>6B</issue><spage>4103</spage><epage>4113</epage><pages>4103-4113</pages><issn>0250-7005</issn><eissn>1791-7530</eissn><abstract>Background: Cyclooxygenase (COX) inhibitors are reported to exert anti-proliferative and pro-apoptotic effects on cancer. The effects of COX inhibitors on oral squamous cell carcinoma (SCC) and survivin expression were assessed. Materials and Methods: Primary oral SCC were analyzed immunohistochemically, and oral SCC cell lines were assessed using RT-PCR, Western blot, cell proliferation and apoptosis assays, following treatment with various COX inhibitors, SiRNA against survivin, or survivin forced expression. Results: Survivin was expressed in all studied tumors. SiRNA against survivin or treatment with sulindac, but not other COX inhibitors, decreased survivin expression and tumor cell proliferation and increased apoptosis. Forced expression of survivin attenuated sulindac's effects. Conclusion: Survivin is implicated as a marker and treatment target in oral SCC, inhibition of which causes reduction of cell proliferation and induction of apoptosis. Down-regulation of survivin expression by sulindac provides an explanation for its antineoplastic effects.</abstract><cop>Attiki</cop><pub>International Institute of Anticancer Research</pub><pmid>17201121</pmid><tpages>11</tpages></addata></record>
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subjects Apoptosis - drug effects
Base Sequence
Biological and medical sciences
Carcinoma, Squamous Cell - metabolism
Carcinoma, Squamous Cell - pathology
Cell Proliferation - drug effects
Cyclooxygenase Inhibitors - pharmacology
DNA Primers
Down-Regulation - drug effects
Humans
Inhibitor of Apoptosis Proteins
Medical sciences
Microtubule-Associated Proteins - antagonists & inhibitors
Microtubule-Associated Proteins - metabolism
Mouth Neoplasms - metabolism
Mouth Neoplasms - pathology
Neoplasm Proteins - antagonists & inhibitors
Neoplasm Proteins - metabolism
Oligonucleotide Array Sequence Analysis
Otorhinolaryngology. Stomatology
RNA, Small Interfering
Sulindac - pharmacology
Tumors
Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology
title COX-independent Antineoplastic Effects of Sulindac in Oral Cancer are Mediated by Survivin Down-regulation
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