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Water Extract of Sporoderm-Broken Spores of Ganoderma lucidum Induces Osteosarcoma Apoptosis and Restricts Autophagic Flux

Identifieur interne : 000278 ( Main/Exploration ); précédent : 000277; suivant : 000279

Water Extract of Sporoderm-Broken Spores of Ganoderma lucidum Induces Osteosarcoma Apoptosis and Restricts Autophagic Flux

Auteurs : Wenkan Zhang [République populaire de Chine] ; Zhong Lei [République populaire de Chine] ; Jiahong Meng [République populaire de Chine] ; Guoqi Li [République populaire de Chine] ; Yuxiang Zhang [République populaire de Chine] ; Jiaming He [République populaire de Chine] ; Weiqi Yan [République populaire de Chine]

Source :

RBID : PMC:6942530

Abstract

Purpose

Osteosarcoma (OS) is a malignant bone tumor with easy metastasis and poor prognosis. Ganoderma lucidum (G. lucidum), a traditional Chinese medicine, was reported playing a critical role in suppressing multiple tumor progress. So we wanted to investigate the effects and molecular mechanisms of water extract of sporoderm-broken spores of G. lucidum (BSGLWE) on osteosarcoma.

Methods

In vitro, the effects on cell proliferation of BSGLWE in osteosarcoma cells were detected by CCK-8, colony formation assay and flow cytometry; migration ability of osteosarcoma cells was evaluated by cell scratch and transwell assays. Cell apoptosis and autophagy were tested by transmission electron microscopy (TEM). Potential signaling pathways were detected by Western blotting and immunofluorescence. In xenograft orthotopic model, the luminescence intensity measured by an in vivo bioluminescence imaging system, and the expression of related proteins in tumor cells were assessed by IHC analysis.

Results

BSGLWE suppressed the proliferation and migration of osteosarcoma cells in a dose-dependent manner, and osteosarcoma cell cycle progression at the G2/M phase was arrested by the BSGLWE. In addition, increased apoptosis-related protein expression meant BSFLWE induced caspase-dependent apoptosis of osteosarcoma cells. TEM results indicated that BSGLWE promoted the formation of apoptotic bodies and autophagosomes in HOS and U2 cells. Western blotting or immunofluorescence and rescue assay revealed that BSGLWE blocked autophagic flux by inducing initiation of autophagy and increasing autophagosome accumulation of osteosarcoma cells. BSGLWE not only repressed the angiogenesis in the mouse model, but also induced apoptosis and blocked autophagy in vivo.

Conclusion

BSGLWE inhibits osteosarcoma progression.


Url:
DOI: 10.2147/OTT.S226850
PubMed: 32021244
PubMed Central: 6942530


Affiliations:


Links toward previous steps (curation, corpus...)


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<title xml:lang="en" level="a" type="main">Water Extract of Sporoderm-Broken Spores of
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Induces Osteosarcoma Apoptosis and Restricts Autophagic Flux</title>
<author>
<name sortKey="Zhang, Wenkan" sort="Zhang, Wenkan" uniqKey="Zhang W" first="Wenkan" last="Zhang">Wenkan Zhang</name>
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<addr-line>Zhejiang</addr-line>
<addr-line>310009</addr-line>
,
<country>People’s Republic of China</country>
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<country xml:lang="fr">République populaire de Chine</country>
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<name sortKey="Meng, Jiahong" sort="Meng, Jiahong" uniqKey="Meng J" first="Jiahong" last="Meng">Jiahong Meng</name>
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,
<addr-line>Zhejiang</addr-line>
<addr-line>310009</addr-line>
,
<country>People’s Republic of China</country>
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<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<institution>Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine</institution>
,
<addr-line>Hangzhou</addr-line>
,
<addr-line>Zhejiang</addr-line>
<addr-line>310009</addr-line>
,
<country>People’s Republic of China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
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<author>
<name sortKey="Li, Guoqi" sort="Li, Guoqi" uniqKey="Li G" first="Guoqi" last="Li">Guoqi Li</name>
<affiliation wicri:level="1">
<nlm:aff id="AFF0001">
<institution>Department of Orthopedics Research Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine</institution>
,
<addr-line>Hangzhou</addr-line>
,
<addr-line>Zhejiang</addr-line>
<addr-line>310009</addr-line>
,
<country>People’s Republic of China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<nlm:aff id="AFF0002">
<institution>Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine</institution>
,
<addr-line>Hangzhou</addr-line>
,
<addr-line>Zhejiang</addr-line>
<addr-line>310009</addr-line>
,
<country>People’s Republic of China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
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<author>
<name sortKey="Zhang, Yuxiang" sort="Zhang, Yuxiang" uniqKey="Zhang Y" first="Yuxiang" last="Zhang">Yuxiang Zhang</name>
<affiliation wicri:level="1">
<nlm:aff id="AFF0001">
<institution>Department of Orthopedics Research Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine</institution>
,
<addr-line>Hangzhou</addr-line>
,
<addr-line>Zhejiang</addr-line>
<addr-line>310009</addr-line>
,
<country>People’s Republic of China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<affiliation wicri:level="1">
<nlm:aff id="AFF0002">
<institution>Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine</institution>
,
<addr-line>Hangzhou</addr-line>
,
<addr-line>Zhejiang</addr-line>
<addr-line>310009</addr-line>
,
<country>People’s Republic of China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author>
<name sortKey="He, Jiaming" sort="He, Jiaming" uniqKey="He J" first="Jiaming" last="He">Jiaming He</name>
<affiliation wicri:level="1">
<nlm:aff id="AFF0001">
<institution>Department of Orthopedics Research Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine</institution>
,
<addr-line>Hangzhou</addr-line>
,
<addr-line>Zhejiang</addr-line>
<addr-line>310009</addr-line>
,
<country>People’s Republic of China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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,
<addr-line>Hangzhou</addr-line>
,
<addr-line>Zhejiang</addr-line>
<addr-line>310009</addr-line>
,
<country>People’s Republic of China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
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<author>
<name sortKey="Yan, Weiqi" sort="Yan, Weiqi" uniqKey="Yan W" first="Weiqi" last="Yan">Weiqi Yan</name>
<affiliation wicri:level="1">
<nlm:aff id="AFF0001">
<institution>Department of Orthopedics Research Institute, The Second Affiliated Hospital, Zhejiang University School of Medicine</institution>
,
<addr-line>Hangzhou</addr-line>
,
<addr-line>Zhejiang</addr-line>
<addr-line>310009</addr-line>
,
<country>People’s Republic of China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
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<nlm:aff id="AFF0002">
<institution>Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine</institution>
,
<addr-line>Hangzhou</addr-line>
,
<addr-line>Zhejiang</addr-line>
<addr-line>310009</addr-line>
,
<country>People’s Republic of China</country>
</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
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</analytic>
<series>
<title level="j">OncoTargets and therapy</title>
<idno type="eISSN">1178-6930</idno>
<imprint>
<date when="2019">2019</date>
</imprint>
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<front>
<div type="abstract" xml:lang="en">
<sec id="S2001">
<title>Purpose</title>
<p>Osteosarcoma (OS) is a malignant bone tumor with easy metastasis and poor prognosis.
<italic>Ganoderma lucidum</italic>
(
<italic>G. lucidum</italic>
), a traditional Chinese medicine, was reported playing a critical role in suppressing multiple tumor progress. So we wanted to investigate the effects and molecular mechanisms of water extract of sporoderm-broken spores of
<italic>G. lucidum</italic>
(BSGLWE) on osteosarcoma.</p>
</sec>
<sec id="S2002">
<title>Methods</title>
<p>In vitro, the effects on cell proliferation of BSGLWE in osteosarcoma cells were detected by CCK-8, colony formation assay and flow cytometry; migration ability of osteosarcoma cells was evaluated by cell scratch and transwell assays. Cell apoptosis and autophagy were tested by transmission electron microscopy (TEM). Potential signaling pathways were detected by Western blotting and immunofluorescence. In xenograft orthotopic model, the luminescence intensity measured by an in vivo bioluminescence imaging system, and the expression of related proteins in tumor cells were assessed by IHC analysis.</p>
</sec>
<sec id="S2003">
<title>Results</title>
<p>BSGLWE suppressed the proliferation and migration of osteosarcoma cells in a dose-dependent manner, and osteosarcoma cell cycle progression at the G2/M phase was arrested by the BSGLWE. In addition, increased apoptosis-related protein expression meant BSFLWE induced caspase-dependent apoptosis of osteosarcoma cells. TEM results indicated that BSGLWE promoted the formation of apoptotic bodies and autophagosomes in HOS and U2 cells. Western blotting or immunofluorescence and rescue assay revealed that BSGLWE blocked autophagic flux by inducing initiation of autophagy and increasing autophagosome accumulation of osteosarcoma cells. BSGLWE not only repressed the angiogenesis in the mouse model, but also induced apoptosis and blocked autophagy in vivo.</p>
</sec>
<sec id="S2004">
<title>Conclusion</title>
<p>BSGLWE inhibits osteosarcoma progression.</p>
</sec>
</div>
</front>
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<name sortKey="Zhang, Wenkan" sort="Zhang, Wenkan" uniqKey="Zhang W" first="Wenkan" last="Zhang">Wenkan Zhang</name>
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<name sortKey="He, Jiaming" sort="He, Jiaming" uniqKey="He J" first="Jiaming" last="He">Jiaming He</name>
<name sortKey="He, Jiaming" sort="He, Jiaming" uniqKey="He J" first="Jiaming" last="He">Jiaming He</name>
<name sortKey="Lei, Zhong" sort="Lei, Zhong" uniqKey="Lei Z" first="Zhong" last="Lei">Zhong Lei</name>
<name sortKey="Lei, Zhong" sort="Lei, Zhong" uniqKey="Lei Z" first="Zhong" last="Lei">Zhong Lei</name>
<name sortKey="Li, Guoqi" sort="Li, Guoqi" uniqKey="Li G" first="Guoqi" last="Li">Guoqi Li</name>
<name sortKey="Li, Guoqi" sort="Li, Guoqi" uniqKey="Li G" first="Guoqi" last="Li">Guoqi Li</name>
<name sortKey="Meng, Jiahong" sort="Meng, Jiahong" uniqKey="Meng J" first="Jiahong" last="Meng">Jiahong Meng</name>
<name sortKey="Meng, Jiahong" sort="Meng, Jiahong" uniqKey="Meng J" first="Jiahong" last="Meng">Jiahong Meng</name>
<name sortKey="Yan, Weiqi" sort="Yan, Weiqi" uniqKey="Yan W" first="Weiqi" last="Yan">Weiqi Yan</name>
<name sortKey="Yan, Weiqi" sort="Yan, Weiqi" uniqKey="Yan W" first="Weiqi" last="Yan">Weiqi Yan</name>
<name sortKey="Zhang, Wenkan" sort="Zhang, Wenkan" uniqKey="Zhang W" first="Wenkan" last="Zhang">Wenkan Zhang</name>
<name sortKey="Zhang, Yuxiang" sort="Zhang, Yuxiang" uniqKey="Zhang Y" first="Yuxiang" last="Zhang">Yuxiang Zhang</name>
<name sortKey="Zhang, Yuxiang" sort="Zhang, Yuxiang" uniqKey="Zhang Y" first="Yuxiang" last="Zhang">Yuxiang Zhang</name>
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