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Autophagy Inhibition Stimulates Apoptosis in Oesophageal Squamous Cell Carcinoma Treated with Fasudil.

Identifieur interne : 000121 ( PubMed/Corpus ); précédent : 000120; suivant : 000122

Autophagy Inhibition Stimulates Apoptosis in Oesophageal Squamous Cell Carcinoma Treated with Fasudil.

Auteurs : Fa-Jun Xie ; Qiu-Qing Zheng ; Jing Qin ; Ling-Ling Zhang ; Na Han ; Wei-Min Mao

Source :

Journal of Cancer [ 1837-9664 ] ; 2018.

RBID : pubmed:29581784

Abstract

Fasudil has been proven to be a promising chemotherapeutic drug for various malignancies. However, the potential anticancer effects of fasudil in oesophageal squamous cell carcinoma (ESCC) remain to be established. We confirmed the RhoA activity is inhibited by fasudil in ESCC cells. Then measured the effects of fasudil on apoptosis and autophagy in ESCC. Our study showed fasudil could both induce ESCCs apoptosis and autophagy, and when fasudil-induced autophagy was inhibited by knockdown of the essential autophagy genes (Beclin 1 or ATG7), and pharmacologic agent (chloroquine) treatment, both treatments also significantly sensitized ESCC to fasudil-induced apoptosis, reducing cell viability in vitro. Our study showed autophagy inhibitors combined with fasudil could significantly induce ESCC apoptosis, which may provide a novel therapeutic strategy for ESCC.

DOI: 10.7150/jca.23388
PubMed: 29581784

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<author><name sortKey="Xie, Fa Jun" sort="Xie, Fa Jun" uniqKey="Xie F" first="Fa-Jun" last="Xie">Fa-Jun Xie</name>
<affiliation><nlm:affiliation>Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, China.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Zheng, Qiu Qing" sort="Zheng, Qiu Qing" uniqKey="Zheng Q" first="Qiu-Qing" last="Zheng">Qiu-Qing Zheng</name>
<affiliation><nlm:affiliation>Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Oesophagus), Hangzhou 310022, China.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Qin, Jing" sort="Qin, Jing" uniqKey="Qin J" first="Jing" last="Qin">Jing Qin</name>
<affiliation><nlm:affiliation>Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, China.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Zhang, Ling Ling" sort="Zhang, Ling Ling" uniqKey="Zhang L" first="Ling-Ling" last="Zhang">Ling-Ling Zhang</name>
<affiliation><nlm:affiliation>Department of Medical Oncology, Peking University International Hospital, Beijing 102206, China.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Han, Na" sort="Han, Na" uniqKey="Han N" first="Na" last="Han">Na Han</name>
<affiliation><nlm:affiliation>Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, China.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Mao, Wei Min" sort="Mao, Wei Min" uniqKey="Mao W" first="Wei-Min" last="Mao">Wei-Min Mao</name>
<affiliation><nlm:affiliation>Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Oesophagus), Hangzhou 310022, China.</nlm:affiliation>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Autophagy Inhibition Stimulates Apoptosis in Oesophageal Squamous Cell Carcinoma Treated with Fasudil.</title>
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<affiliation><nlm:affiliation>Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, China.</nlm:affiliation>
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<author><name sortKey="Zheng, Qiu Qing" sort="Zheng, Qiu Qing" uniqKey="Zheng Q" first="Qiu-Qing" last="Zheng">Qiu-Qing Zheng</name>
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<author><name sortKey="Zhang, Ling Ling" sort="Zhang, Ling Ling" uniqKey="Zhang L" first="Ling-Ling" last="Zhang">Ling-Ling Zhang</name>
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<author><name sortKey="Han, Na" sort="Han, Na" uniqKey="Han N" first="Na" last="Han">Na Han</name>
<affiliation><nlm:affiliation>Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, China.</nlm:affiliation>
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<front><div type="abstract" xml:lang="en">Fasudil has been proven to be a promising chemotherapeutic drug for various malignancies. However, the potential anticancer effects of fasudil in oesophageal squamous cell carcinoma (ESCC) remain to be established. We confirmed the RhoA activity is inhibited by fasudil in ESCC cells. Then measured the effects of fasudil on apoptosis and autophagy in ESCC. Our study showed fasudil could both induce ESCCs apoptosis and autophagy, and when fasudil-induced autophagy was inhibited by knockdown of the essential autophagy genes (Beclin 1 or ATG7), and pharmacologic agent (chloroquine) treatment, both treatments also significantly sensitized ESCC to fasudil-induced apoptosis, reducing cell viability in vitro. Our study showed autophagy inhibitors combined with fasudil could significantly induce ESCC apoptosis, which may provide a novel therapeutic strategy for ESCC.</div>
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<DateRevised><Year>2019</Year>
<Month>11</Month>
<Day>20</Day>
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<JournalIssue CitedMedium="Print"><Volume>9</Volume>
<Issue>6</Issue>
<PubDate><Year>2018</Year>
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<Title>Journal of Cancer</Title>
<ISOAbbreviation>J Cancer</ISOAbbreviation>
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<ArticleTitle>Autophagy Inhibition Stimulates Apoptosis in Oesophageal Squamous Cell Carcinoma Treated with Fasudil.</ArticleTitle>
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<Abstract><AbstractText>Fasudil has been proven to be a promising chemotherapeutic drug for various malignancies. However, the potential anticancer effects of fasudil in oesophageal squamous cell carcinoma (ESCC) remain to be established. We confirmed the RhoA activity is inhibited by fasudil in ESCC cells. Then measured the effects of fasudil on apoptosis and autophagy in ESCC. Our study showed fasudil could both induce ESCCs apoptosis and autophagy, and when fasudil-induced autophagy was inhibited by knockdown of the essential autophagy genes (Beclin 1 or ATG7), and pharmacologic agent (chloroquine) treatment, both treatments also significantly sensitized ESCC to fasudil-induced apoptosis, reducing cell viability in vitro. Our study showed autophagy inhibitors combined with fasudil could significantly induce ESCC apoptosis, which may provide a novel therapeutic strategy for ESCC.</AbstractText>
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<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Xie</LastName>
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<AffiliationInfo><Affiliation>Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, China.</Affiliation>
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<AffiliationInfo><Affiliation>Department of Thoracic Surgery, Zhejiang Cancer Hospital, Hangzhou 310022, China.</Affiliation>
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<MedlineJournalInfo><Country>Australia</Country>
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<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Apoptosis</Keyword>
<Keyword MajorTopicYN="N">Autophagy</Keyword>
<Keyword MajorTopicYN="N">Fasudil</Keyword>
<Keyword MajorTopicYN="N">Oesophageal squamous cell carcinoma</Keyword>
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<CoiStatement>Competing Interests: The authors have declared that no competing interest exists.</CoiStatement>
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Autophagy Inhibition Stimulates Apoptosis in Oesophageal Squamous Cell Carcinoma Treated with Fasudil.

Autophagy Inhibition Stimulates Apoptosis in Oesophageal Squamous Cell Carcinoma Treated with Fasudil.

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Abstract

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