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<title xml:lang="en">Effect of silencing S-phase kinase-associated protein 2 on chemosensitivity to temozolomide of human glioma cells U251</title>
<author>
<name sortKey="Liu, Yue" sort="Liu, Yue" uniqKey="Liu Y" first="Yue" last="Liu">Yue Liu</name>
</author>
<author>
<name sortKey="Tang, Zhen Gang" sort="Tang, Zhen Gang" uniqKey="Tang Z" first="Zhen-Gang" last="Tang">Zhen-Gang Tang</name>
</author>
<author>
<name sortKey="Yang, Jian Quan" sort="Yang, Jian Quan" uniqKey="Yang J" first="Jian-Quan" last="Yang">Jian-Quan Yang</name>
</author>
<author>
<name sortKey="Zhou, Yi" sort="Zhou, Yi" uniqKey="Zhou Y" first="Yi" last="Zhou">Yi Zhou</name>
</author>
<author>
<name sortKey="Lin, Yi" sort="Lin, Yi" uniqKey="Lin Y" first="Yi" last="Lin">Yi Lin</name>
</author>
<author>
<name sortKey="Lv, Wei" sort="Lv, Wei" uniqKey="Lv W" first="Wei" last="Lv">Wei Lv</name>
</author>
<author>
<name sortKey="Wang, Guo Bin" sort="Wang, Guo Bin" uniqKey="Wang G" first="Guo-Bin" last="Wang">Guo-Bin Wang</name>
</author>
<author>
<name sortKey="Li, Cai Li" sort="Li, Cai Li" uniqKey="Li C" first="Cai-Li" last="Li">Cai-Li Li</name>
</author>
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<idno type="wicri:source">PMC</idno>
<idno type="pmid">31105854</idno>
<idno type="pmc">6511802</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511802</idno>
<idno type="RBID">PMC:6511802</idno>
<date when="2019">2019</date>
<idno type="wicri:Area/Pmc/Corpus">000351</idno>
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<title xml:lang="en" level="a" type="main">Effect of silencing S-phase kinase-associated protein 2 on chemosensitivity to temozolomide of human glioma cells U251</title>
<author>
<name sortKey="Liu, Yue" sort="Liu, Yue" uniqKey="Liu Y" first="Yue" last="Liu">Yue Liu</name>
</author>
<author>
<name sortKey="Tang, Zhen Gang" sort="Tang, Zhen Gang" uniqKey="Tang Z" first="Zhen-Gang" last="Tang">Zhen-Gang Tang</name>
</author>
<author>
<name sortKey="Yang, Jian Quan" sort="Yang, Jian Quan" uniqKey="Yang J" first="Jian-Quan" last="Yang">Jian-Quan Yang</name>
</author>
<author>
<name sortKey="Zhou, Yi" sort="Zhou, Yi" uniqKey="Zhou Y" first="Yi" last="Zhou">Yi Zhou</name>
</author>
<author>
<name sortKey="Lin, Yi" sort="Lin, Yi" uniqKey="Lin Y" first="Yi" last="Lin">Yi Lin</name>
</author>
<author>
<name sortKey="Lv, Wei" sort="Lv, Wei" uniqKey="Lv W" first="Wei" last="Lv">Wei Lv</name>
</author>
<author>
<name sortKey="Wang, Guo Bin" sort="Wang, Guo Bin" uniqKey="Wang G" first="Guo-Bin" last="Wang">Guo-Bin Wang</name>
</author>
<author>
<name sortKey="Li, Cai Li" sort="Li, Cai Li" uniqKey="Li C" first="Cai-Li" last="Li">Cai-Li Li</name>
</author>
</analytic>
<series>
<title level="j">American Journal of Translational Research</title>
<idno type="eISSN">1943-8141</idno>
<imprint>
<date when="2019">2019</date>
</imprint>
</series>
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<front>
<div type="abstract" xml:lang="en">
<p>Objective: To examine the effect of silencing SKP2 on chemosensitivity of human glioma cells U251 to temozolomide (TMZ). Methods: Adenoviruses harbouring shRNA targeting SKP2 (i.e. Ad-shSKP2) and non-targeting scrambled shRNA (i.e. Ad-shNC) were used to infect U251 cells. The transduced cells were then treated with TMZ. Cell viability after treatment was assayed using CCK8; while cell cycle and apoptosis were examined using flow cytometry. To study the effect of silencing SKP2 on autophagy in U251, we co-transduced the cells with Ad-mRFP-LC3 and Ad-shSKP2/Ad-shNC. The expression of autophagy marker LC3 after TMZ treatment was studied using microscopy and Western blotting assays. Results: The cytotoxicity of TMZ (i.e. 20-100 µM) was more significantly seen in Ad-shSKP2-transduced U251 cells than in the Ad-shNC-transduced U251 cells. The IC
<sub>50</sub>
values in shSKP2-U251 were significantly lower than those of the shNC-U251 (
<italic>P</italic>
< 0.05). Both TMZ and Ad-shSKP2 alone increased apoptosis and promoted expression of LC3 in U251. Combined treatment of Ad-shSKP2 and TMZ further elevated apoptosis and LC3 expression. Conclusion: Silencing SKP2 in U251 cells increased chemosensitivity to TMZ that was accompanied with enhanced apoptosis and autophagy. Targeting SKP2 may be a potential approach to potentiate TMZ treatment in patients with glioma.</p>
</div>
</front>
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<pmc article-type="research-article">
<pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Am J Transl Res</journal-id>
<journal-id journal-id-type="iso-abbrev">Am J Transl Res</journal-id>
<journal-id journal-id-type="publisher-id">ajtr</journal-id>
<journal-title-group>
<journal-title>American Journal of Translational Research</journal-title>
</journal-title-group>
<issn pub-type="epub">1943-8141</issn>
<publisher>
<publisher-name>e-Century Publishing Corporation</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">31105854</article-id>
<article-id pub-id-type="pmc">6511802</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Original Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Effect of silencing S-phase kinase-associated protein 2 on chemosensitivity to temozolomide of human glioma cells U251</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Liu</surname>
<given-names>Yue</given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Tang</surname>
<given-names>Zhen-Gang</given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Yang</surname>
<given-names>Jian-Quan</given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Zhou</surname>
<given-names>Yi</given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lin</surname>
<given-names>Yi</given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lv</surname>
<given-names>Wei</given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wang</surname>
<given-names>Guo-Bin</given-names>
</name>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Li</surname>
<given-names>Cai-Li</given-names>
</name>
</contrib>
<aff>
<institution>Department of Neurosurgery, Renmin Hospital, Hubei University of Medicine</institution>
<addr-line>Shiyan, Hubei, P.R. China</addr-line>
</aff>
</contrib-group>
<author-notes>
<corresp>
<bold>Address correspondence to:</bold>
Cai-Li Li, Department of Neurosurgery, Renmin Hospital, Hubei University of Medicine, No. 39 Middle Chaoyang Road, Shiyan 442000, Hubei, P. R. China. Tel: +86-13597883520; E-mail:
<email>licailili@163.com</email>
</corresp>
</author-notes>
<pub-date pub-type="collection">
<year>2019</year>
</pub-date>
<pub-date pub-type="epub">
<day>15</day>
<month>4</month>
<year>2019</year>
</pub-date>
<volume>11</volume>
<issue>4</issue>
<fpage>2470</fpage>
<lpage>2476</lpage>
<history>
<date date-type="received">
<day>19</day>
<month>12</month>
<year>2018</year>
</date>
<date date-type="accepted">
<day>16</day>
<month>1</month>
<year>2019</year>
</date>
</history>
<permissions>
<copyright-statement>AJTR Copyright © 2019</copyright-statement>
<copyright-year>2019</copyright-year>
</permissions>
<abstract>
<p>Objective: To examine the effect of silencing SKP2 on chemosensitivity of human glioma cells U251 to temozolomide (TMZ). Methods: Adenoviruses harbouring shRNA targeting SKP2 (i.e. Ad-shSKP2) and non-targeting scrambled shRNA (i.e. Ad-shNC) were used to infect U251 cells. The transduced cells were then treated with TMZ. Cell viability after treatment was assayed using CCK8; while cell cycle and apoptosis were examined using flow cytometry. To study the effect of silencing SKP2 on autophagy in U251, we co-transduced the cells with Ad-mRFP-LC3 and Ad-shSKP2/Ad-shNC. The expression of autophagy marker LC3 after TMZ treatment was studied using microscopy and Western blotting assays. Results: The cytotoxicity of TMZ (i.e. 20-100 µM) was more significantly seen in Ad-shSKP2-transduced U251 cells than in the Ad-shNC-transduced U251 cells. The IC
<sub>50</sub>
values in shSKP2-U251 were significantly lower than those of the shNC-U251 (
<italic>P</italic>
< 0.05). Both TMZ and Ad-shSKP2 alone increased apoptosis and promoted expression of LC3 in U251. Combined treatment of Ad-shSKP2 and TMZ further elevated apoptosis and LC3 expression. Conclusion: Silencing SKP2 in U251 cells increased chemosensitivity to TMZ that was accompanied with enhanced apoptosis and autophagy. Targeting SKP2 may be a potential approach to potentiate TMZ treatment in patients with glioma.</p>
</abstract>
<kwd-group>
<kwd>Glioma</kwd>
<kwd>S-phase kinase-associated protein 2 (SKP2)</kwd>
<kwd>temozolomide (TMZ)</kwd>
<kwd>chemosensitivity</kwd>
<kwd>autophagy</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>

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