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Connexin 43 (cx43) enhances chemotherapy-induced apoptosis in human glioblastoma cells.
- Source :
-
International journal of cancer [Int J Cancer] 2001 Apr 01; Vol. 92 (1), pp. 130-8. - Publication Year :
- 2001
-
Abstract
- Stable re-expression of connexin 43 (cx43) in human glioblastoma suppresses transformation and tumorigenicity. The present study was designed to examine the role of cx43 in chemotherapy-induced apoptosis. Expression of cx43 in human glioblastoma cells significantly increased sensitivity to several common chemotherapeutic agents, including etoposide, paclitaxel (Taxol) and doxorubicin, compared with control-transfected cells. The increased sensitivity to chemotherapeutic agents resulted from apoptosis as evidenced by Hoechst dye staining, TUNEL assay and annexin V assay. These cx43-mediated effects were coupled with decreased expression of the specific apoptosis inhibitor bcl-2. Over-expression of bcl-2 in cx43-transfected cells partially confers the resistance to apoptosis induced by etoposide, suggesting that the cx43-mediated apoptosis to chemotherapeutic agents is regulated in part through the down-regulation of bcl-2 expression. Furthermore, the cx43-mediated apoptosis in response to chemotherapeutic drugs may not be linked to increased gap junctional communication in cx43-transfected cells. Our results demonstrate a new role of cx43 in the mediation of apoptosis during chemotherapy.<br /> (Copyright 2001 Wiley-Liss, Inc.)
- Subjects :
- Apoptosis genetics
Blotting, Western
Cell Survival drug effects
Connexin 43 genetics
Drug Interactions
Etoposide pharmacology
Flow Cytometry
Fluorescent Dyes
G2 Phase drug effects
Gap Junctions pathology
Gene Expression Regulation drug effects
Humans
In Situ Nick-End Labeling
Isoquinolines
Proto-Oncogene Proteins c-bcl-2 metabolism
Transfection
Tumor Cells, Cultured
Antineoplastic Agents pharmacology
Apoptosis drug effects
Connexin 43 pharmacology
Glioblastoma pathology
Subjects
Details
- Language :
- English
- ISSN :
- 0020-7136
- Volume :
- 92
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- International journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 11279616