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Article: Lovastatin enhances cytotoxicity of temozolomide via impairing autophagic flux in glioblastoma cells

TitleLovastatin enhances cytotoxicity of temozolomide via impairing autophagic flux in glioblastoma cells
Authors
Issue Date2019
PublisherHindawi Publishing Corporation. The Journal's web site is located at http://www.hindawi.com/journals/jbb/index.html
Citation
BioMed Research International, 2019, v. 2019, p. article no. 2710693 How to Cite?
AbstractDrug resistance to temozolomide (TMZ) contributes to the majority of tumor recurrence and treatment failure in patients with glioblastoma multiforme (GBM). Autophagy has been reported to play a role in chemoresistance in various types of cancer, including GBM. The anticancer effect of statins is arousing great research interests and has been demonstrated to modulate autophagic function. In this study, we investigated the combinational effects of lovastatin and TMZ on treating U87 and U251 GBM cell lines. Cytotoxicity was measured by MTT and colony formation assays; apoptosis was measured by flow cytometry; the cellular autophagic function was detected by the EGFP-mRFP-LC3 reporter and western blot assay. The results showed that lovastatin might enhance the cytotoxicity of TMZ, increase the TMZ-induced cellular apoptosis, and impair the autophagic flux in GBM cells. Lovastatin triggered autophagy initiation possibly by inhibiting the Akt/mTOR signaling pathway. Moreover, lovastatin might impair the autophagosome-lysosome fusion machinery by suppressing LAMP2 and dynein. These results suggested that lovastatin could enhance the chemotherapy efficacy of TMZ in treating GBM cells. The mechanism may be associated with impaired autophagic flux and thereby the enhancement of cellular apoptosis. Combining TMZ with lovastatin could be a promising strategy for GBM treatment.
Persistent Identifierhttp://hdl.handle.net/10722/278283
ISSN
2019 Impact Factor: 2.276
2015 SCImago Journal Rankings: 0.725
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorZHU, Z-
dc.contributor.authorZhang, P-
dc.contributor.authorLI, N-
dc.contributor.authorKIANG, KMY-
dc.contributor.authorCHENG, SY-
dc.contributor.authorWONG, VKW-
dc.contributor.authorLeung, GKK-
dc.date.accessioned2019-10-04T08:11:01Z-
dc.date.available2019-10-04T08:11:01Z-
dc.date.issued2019-
dc.identifier.citationBioMed Research International, 2019, v. 2019, p. article no. 2710693-
dc.identifier.issn2314-6133-
dc.identifier.urihttp://hdl.handle.net/10722/278283-
dc.description.abstractDrug resistance to temozolomide (TMZ) contributes to the majority of tumor recurrence and treatment failure in patients with glioblastoma multiforme (GBM). Autophagy has been reported to play a role in chemoresistance in various types of cancer, including GBM. The anticancer effect of statins is arousing great research interests and has been demonstrated to modulate autophagic function. In this study, we investigated the combinational effects of lovastatin and TMZ on treating U87 and U251 GBM cell lines. Cytotoxicity was measured by MTT and colony formation assays; apoptosis was measured by flow cytometry; the cellular autophagic function was detected by the EGFP-mRFP-LC3 reporter and western blot assay. The results showed that lovastatin might enhance the cytotoxicity of TMZ, increase the TMZ-induced cellular apoptosis, and impair the autophagic flux in GBM cells. Lovastatin triggered autophagy initiation possibly by inhibiting the Akt/mTOR signaling pathway. Moreover, lovastatin might impair the autophagosome-lysosome fusion machinery by suppressing LAMP2 and dynein. These results suggested that lovastatin could enhance the chemotherapy efficacy of TMZ in treating GBM cells. The mechanism may be associated with impaired autophagic flux and thereby the enhancement of cellular apoptosis. Combining TMZ with lovastatin could be a promising strategy for GBM treatment.-
dc.languageeng-
dc.publisherHindawi Publishing Corporation. The Journal's web site is located at http://www.hindawi.com/journals/jbb/index.html-
dc.relation.ispartofBioMed Research International-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleLovastatin enhances cytotoxicity of temozolomide via impairing autophagic flux in glioblastoma cells-
dc.typeArticle-
dc.identifier.emailZhang, P: pingder@hku.hk-
dc.identifier.emailLeung, GKK: gkkleung@hku.hk-
dc.identifier.authorityLeung, GKK=rp00522-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1155/2019/2710693-
dc.identifier.pmid31662972-
dc.identifier.pmcidPMC6778891-
dc.identifier.scopuseid_2-s2.0-85073143302-
dc.identifier.hkuros306776-
dc.identifier.volume2019-
dc.identifier.spagearticle no. 2710693-
dc.identifier.epagearticle no. 2710693-
dc.publisher.placeUnited States-

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