Abstract | BACKGROUND: In the current study, the authors sought to identify the molecular mechanisms underlying the chemoresistance of lung cancer stem or initiation cells (cancer stem cells). METHODS: A549 lung cancer cells before and after selective enrichment of a subpopulation of cancer stem cells were treated with superoxide and traditional chemotherapeutics to determine their sensitivity or resistance to these cytotoxic agents. Apoptotic activity was measured using a variety of fluorescence-based and biochemical techniques. Specific pathways involved in the chemoresistance of cancer stem cell-enriched lung cancer cells were analyzed with Western blotting and pharmacologic targeting therapy in a xenograft model. RESULTS: CONCLUSIONS: The authors' data demonstrate that lung cancer stem cells have elevated levels of activated Hsp27 upon treatment with superoxide and traditional chemotherapy. When combined with chemotoxic agents, blockage of Hsp27 decreased the survival of lung cancer stem cells, which otherwise were resistant to traditional chemotherapy.
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Authors | Han-Shui Hsu, Jiun-Han Lin, Wen-Chien Huang, Tien-Wei Hsu, Kelly Su, Shih-Hwa Chiou, Yo-Ting Tsai, Shih-Chieh Hung |
Journal | Cancer
(Cancer)
Vol. 117
Issue 7
Pg. 1516-28
(Apr 01 2011)
ISSN: 0008-543X [Print] United States |
PMID | 21425153
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2010 American Cancer Society. |
Chemical References |
- Antineoplastic Agents
- HSP27 Heat-Shock Proteins
- Superoxides
- Quercetin
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Topics |
- Adenocarcinoma
(drug therapy, metabolism, pathology)
- Animals
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects)
- Cell Line, Tumor
- Drug Resistance, Neoplasm
- HSP27 Heat-Shock Proteins
(antagonists & inhibitors, metabolism)
- Humans
- Lung Neoplasms
(drug therapy, metabolism, pathology)
- Mice
- Neoplasm Transplantation
- Neoplastic Stem Cells
(drug effects)
- Quercetin
(pharmacology)
- Signal Transduction
- Superoxides
(pharmacology)
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