Lovastatin Enhances Cytotoxicity of Temozolomide via Impairing Autophagic Flux in Glioblastoma Cells.
Drug 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 aro...
| Publicado en: | BioMed Research International pp. 1 - 13 |
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| Autores principales: | , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
9/23/2019
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=138763576&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 138763576 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23146133 FT2T jtl: BioMed Research International issn: 23146133 maglogo: N pubinfo: dt: 9/23/2019 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 138763576 138763576 138763576 10.1155/2019/2710693 138763576 ppf: 1 ppct: 12 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Lovastatin Enhances Cytotoxicity of Temozolomide via Impairing Autophagic Flux in Glioblastoma Cells. aug: au: Zhu, Zhiyuan Zhang, Pingde Li, Ning Kiang, Karrie Mei Yee Cheng, Stephen Yin Wong, Vincent Kam-Wai Leung, Gilberto Ka-Kit affil: Division of Neurosurgery, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China sug: subj: Drug Resistance, Neoplasm Lovastatin Pharmacodynamics Temozolomide Pharmacodynamics Drug Combinations Drug Synergism Glioma Prevention and Control Cell Line, Tumor Drug Effects Cell Death Drug Effects Human Temozolomide Therapeutic Use Lovastatin Therapeutic Use Biological Assay Methods Colony-Forming Units Assay Flow Cytometry Blotting, Western Transferases Drug Effects Intracellular Signaling Peptides and Proteins Drug Effects Signal Transduction Drug Effects Chemotherapy, Cancer Treatment Outcomes Apoptosis Drug Effects Autophagy Drug Effects ab: Drug 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. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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