Document Detail

Inhibition of autophagy-potentiated chemosensitivity to cisplatin in laryngeal cancer Hep-2 cells.
MedLine Citation:
PMID:  22771248     Owner:  NLM     Status:  Publisher    
OBJECTIVE: The purposes of this study were to determine whether autophagy was involved in cisplatin (CDDP) resistance and to investigate the role of the autophagy in the regulation of chemosensitivity to CDDP in laryngeal cancer Hep-2 cells. METHODS: A WST-1 assay was performed to determine cell viability and cell proliferation. Autophagy activation and proapoptotic effects were characterized using monodansylcadaverine labeling and Hoechest staining, respectively. Western blot analysis was used to detect the expression of apoptotic and autophagy-related genes. Flow cytometry was used to assess cell apoptosis ratio. RESULTS: Exposure to CDDP induced the aggregation of autophagosomes in the cytoplasms of Hep-2 cells and up-regulated the expression of Beclin 1 and LC3II. However, CDDP treatment could not lead to obvious inhibition of cell proliferation, which implies that the autophagy may protect CDDP-treated cells from undergoing cell death. Meanwhile, the WST-1 assay indicated that knockdown of the autophagic gene Beclin 1 sensitized Hep-2 cells to CDDP. Furthermore, CDDP-mediated apoptotic cell death was further potentiated by pretreatment with autophagy inhibitor 3-methyladenine or small interfering RNA against Beclin 1. For the definite mechanism of Beclin 1-enhancing chemosensitivity to CDDP, we found that Beclin1 augmented CDDP-induced apoptotic signaling via enhancing caspase-9 and caspase-3 activity but not caspase-8. CONCLUSION: Our results suggest that functional autophagy in response to CDDP may lead to cell survival in Hep-2 cells, whereas defective autophagy may contribute to CDDP-induced apoptosis in Hep-2 cells. Thus, modulators of autophagy may be used beneficially as adjunctive therapeutic agents during the treatment of laryngeal cancer with CDDP therapy.
Rong Kang; Zan-Hong Wang; Bin-Quan Wang; Chun-Ming Zhang; Wei Gao; Yan Feng; Tao Bai; Hai-Li Zhang; Hui Huang-Pu; Shu-Xin Wen
Related Documents :
16421928 - Self-organized and highly ordered domain structures within swarms of myxococcus xanthus.
18554748 - Dual chemotaxis signalling regulates dictyostelium development: intercellular cyclic am...
22336918 - A new clue to explain resistance to mtor inhibitors.
15048148 - The effect of triethyllead on the motile activity of walker 256 carcinosarcoma cells.
11438548 - Effects of tissue transglutaminase on retinoic acid-induced cellular differentiation an...
18176708 - Immunohistochemical expression of vimentin, calponin and hhf-35 in salivary gland tumors.
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-6
Journal Detail:
Title:  American journal of otolaryngology     Volume:  -     ISSN:  1532-818X     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8000029     Medline TA:  Am J Otolaryngol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Department of Otolaryngology Head and Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan, People's Republic of China.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Mucocele formation under pedicled nasoseptal flap.
Next Document:  Cerebrospinal hepatocyte growth factor levels correlate negatively with disease activity in multiple...