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

Int J Cancer. 2001 Apr 1;92(1):130-8.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Blotting, Western
  • Cell Survival / drug effects
  • Connexin 43 / genetics
  • Connexin 43 / pharmacology*
  • Drug Interactions
  • Etoposide / pharmacology
  • Flow Cytometry
  • Fluorescent Dyes
  • G2 Phase / drug effects
  • Gap Junctions / pathology
  • Gene Expression Regulation / drug effects
  • Glioblastoma / pathology*
  • Humans
  • In Situ Nick-End Labeling
  • Isoquinolines
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Transfection
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • Connexin 43
  • Fluorescent Dyes
  • Isoquinolines
  • Proto-Oncogene Proteins c-bcl-2
  • Etoposide
  • lucifer yellow