The role of gap junctions composed of connexin 43 on the anti-tumor effect induced by etoposide / 中国癌症杂志

ABSTRACT

Background and purpose: Gap junctions(GJ) could enhance cytotoxicity induced by chemotherapeutic agents. However, whether or not GJ composed of connexin 43 (Cx43) could increase etoposide cytotoxicity remains unclear. The aim of this study was to explore the effect of GJ composed of Cx43 on etoposide cytotoxicity in testicular cancer cells. Methods: Eighteen-glycyrrhetinic acid and siRNA were used to inhibit GJ function. Retinoid acid was used to enhance GJ function.“Parachute”dye-coupling assay was used to examine dye spread through GJ composed of Cx43 in MLTC-1 cells. “Standard colony-forming assay” was used to examine cell survivals of MLTC-1 cells treated with etoposide. Results: Assayed by “parachute” dye-coupling assay, the dye spread through GJ in MLTC-1 cells was significantly decreased by 18-glycyrrhetinic acid however increased by retinoid acid. Cx43 expression and GJ function in MLTC-1 cells were inhibited by Cx43-siRNA. Results from “standard colony-forming assay” showed that etoposide cytotoxicity was decreased by 18-glycyrrhetinic acid and siRNA, however enhanced by GJ function enhancer retinoid acid. Conclusion:The function inhibition of Cx43 composed GJ in MLTC-1 cells could decrease etoposide cytotoxicity. The enhancement of GJ composed of Cx43 in MLTC-1 could increase etoposide cytotoxicity.