| Proteasome inhibitor interacts synergistically with autophagy inhibitor to suppress proliferation and induce apoptosis in hepatocellular carcinoma. | |
| | |
MedLine Citation:
|
PMID: 22517429 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
BACKGROUND: The ubiquitin-proteasome system and autophagy-lysosome system are 2 major protein degradation pathways in eukaryotic cells, which are tightly linked to cancer. Proteasome inhibitors have been approved in clinical use against hematologic malignancies, but their application in solid tumors is uncertain. Moreover, the role of autophagy after proteasome inhibition is controversial. METHODS: Two proteasome inhibitors, 2 autophagy inhibitors, and 3 hepatocellular carcinoma (HCC) cell lines were investigated in the current study. In vitro, cell proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell apoptosis was evaluated by flow cytometry analysis of annexin-V/propidium iodide staining, and autophagy was evaluated by green fluorescent protein-light chain 3 (GFP-LC3) redistribution and LC3 Western blot analysis. In vivo, Ki-67 staining was used to detect cell proliferation, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining was used to detect apoptosis, and electron microscopy and p62 immunohistochemical staining were used to detect autophagy. RESULTS: Proteasome inhibitors suppressed proliferation, induced apoptosis, and activated autophagy in HCC cell lines in vitro, and autophagy exerted a protective role after proteasome inhibition. In vivo, anticancer effects of bortezomib on the MHCC-97H orthotopic model (human HCC cells) were different from the effects observed on the Huh-7 subcutaneous model (human HCC cells). The autophagy inhibitor chloroquine interacted synergistically with bortezomib to suppress proliferation and induce apoptosis in both tumor models. CONCLUSIONS: The current results indicated that simultaneous targeting of the proteasome and autophagy pathways may represent a promising method for HCC treatment. Cancer 2012. © 2012 American Cancer Society. |
| | |
Authors:
|
Bo Hui; Ying-Hong Shi; Zhen-Bin Ding; Jian Zhou; Cheng-Yu Gu; Yuan-Fei Peng; Hua Yang; Wei-Ren Liu; Guo-Ming Shi; Jia Fan |
Related Documents
:
|
22563309 - Histamine and neuroinflammation: insights from murine experimental autoimmune encephalo... 22838509 - Antiproliferative activity and apoptosis induction of eucalyptus citriodora resin and i... 22405769 - Th2-inducing cytokines il-4 and il-33 synergistically elicit the expression of transmem... 22558189 - Uterine epithelial cells specifically induce interferon-stimulated genes in response to... 22752759 - Dendritic cells and regulatory t cells in atherosclerosis. 20149459 - Prolonged effect of baff on chicken b cell development revealed by rcas retroviral gene... 9520449 - Cytokine-induced survival of activated t cells in vitro and in vivo. 19027159 - Factors involved in regulating trophoblast fusion: potential role in the development of... 15172219 - Entamoeba histolytica: induction of cyclooxygenase-2 expression during amoebic liver ab... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-4-19 |
Journal Detail:
|
Title: Cancer Volume: - ISSN: 1097-0142 ISO Abbreviation: - Publication Date: 2012 Apr |
Date Detail:
|
Created Date: 2012-4-20 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0374236 Medline TA: Cancer Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
Copyright © 2012 American Cancer Society. |
Affiliation:
|
Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, China; Department of Surgery, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration.
Next Document: Convenient Syntheses and Photophysical Properties of 1-Thio- and 1-Seleno-1,3-Butadiene Fluorophores...