In vitro inhibited effect of gap junction composed of Cx43 in the invasion and metastasis of testicular cancer resistanced to cisplatin

Abstract

The effect of gap junction intercellular communication composed of connexin on cancer invasion/metastasis has been thoroughly explored; however, its effect on testicular cancer resistanced to chemotherapy is still unclear. In this study, we found that the capability of invasion and migration of I-10/DDP (cisplatin (DDP)-resistance) cells were elevated. Furthermore, the expression of Cx43 and the function of gap junction (GJ) in I-10/DDP cells were decreased compared with parental I-10 cells. Pharmacological inhibition of GJs by oleamide (Olea) enhanced invasion and migration. However, enhancement of GJs by retinoic acid (RA) decreased invasion and migration of I-10/DDP cells. To further clarify the invasion/migration inhibited effect of GJ in the testicular cancer resistanced to DDP, GJ function was modulated by overexpression and knockdown of Cx43 expression. Overexpression of Cx43 reduced invasion and migration of I-10/DDP cells. Conversely, knockdown of Cx43 expression increased invasion and migration of I-10/DDP cells. In summary, GJ composed of Cx43 inhibits I-10/DDP cells invasion and migration, and it may become the potential therapeutic target for testicular cancer chemotherapy.