Dexmedetomidine suppresses gap junctional intercellular communication and attenuates the sensitivity of gliocytoma to temozolomid

Abstract

Dexmedetomidine(DEX), an alpha-2 adrenergic agonist which can affect cell-to-cell gap junctions(GJ), is used as an adjuvant analgesic and sedatives in patients with cancer pain, especially in neural cancer patients who concomitantly receiving chemotherapy. GJ may increase the sensitivity of tumor cells to chemotherapeutic agents (Oncol Rep. 2014;31:540-550). It is unknown whether or not DEX may affect the sensitivity of gliocytoma (U87 cell, which richly expresses the GJ protein Connexin43) to temozolomide (TEM, an anticancer agent for gliocytoma) and if DEX exerts its effect via affecting GJ. U87 cells were treated with TEM, respectively at high density (which form GJ) or low density (without GJ formation), for 1 hour in the absence or presence of 3 hours DEX pretreatment prior to applying TEM. TEM toxicity (i.e., reduction of clonogenic cell survival), was assayed by “Standard Clony-forming assay” and GJ function was examined by “Parachute' dye-coupling assay. TEM toxicity was greater at high density than at low density cells (P<0.01), while either oleamide (a GJ inhibitor) or Cx43 siRNA reduced TEM toxicity. Similarly, DEX reduced GJ function and compromised TEM treatment effects, manifested as increases in clonogenic cell survivals at high but not at low cell density. We concluded that DEX reduced TEM cytotoxicity through inhibiting GJ function in gliocytoma.