Connexin 43 (cx43) enhances chemotherapy-induced apoptosis in human glioblastoma cells

Stable re-expression of connexin 43 (cx43) in human glioblastoma suppresses transformation and tumorigenicity. The present study was designed to exami ne the role of cx43 in chemotherapy-induced apoptosis, Expression of cx43 i n human glioblastoma cells significantly increased sensitivity to several c ommon chemotherapeutic agents, including etoposide, paclitaxel (Taxol) and doxorubicin, compared with control-transfected cells. The increased sensiti vity to chemotherapeutic agents resulted from apoptosis as evidenced by Hoe chst dye staining, TUNEL assay and annexin V assay. These cx43-mediated eff ects were coupled with decreased expression of the specific apoptosis inhib itor bcl-2. Overexpression of bcl-2 in cx43-transfected cells partially con fers the resistance to apoptosis induced by etoposide, suggesting that the cx43-mediated apoptosis to chemotherapeutic agents is regulated in part thr ough the down-regulation of bcl-2 expression, Furthermore, the cx43-mediate d apoptosis in response to chemotherapeutic drugs may not be linked to incr eased gap junctional communication in cx43-transfected cells. Our results d emonstrate a new role of cx43 in the mediation of apoptosis during chemothe rapy. (C) 2001 Wiley-Liss, Inc.