GJB2 promotes ovarian cancer progression and cisplatin resistance by upregulating TNC expression.

Cisplatin resistance continues to be a major obstacle in the treatment of ovarian cancer (OC). Gap junction protein β-2 (GJB2), a key member of the connexin family, is well-known for its association with hereditary deafness. However, its role in ovarian cancer chemotherapy resistance remains unexplored. In this study, we found that increased expression of GJB2 was observed in OC patients with poor prognosis and in cisplatin-resistant OC cells. GJB2 knockdown in OVCAR-3 cells inhibited cancer progression and enhanced cisplatin sensitivity via increased drug uptake, while GJB2 overexpression promoted tumor progression and cisplatin resistance. Furthermore, a positive correlation between GJB2 and TNC expression was identified in clinical tissue samples. TNC knockdown in GJB2-overexpressing cells eliminated GJB2-driven OC progression and cisplatin resistance. Finally, epicatechin enhanced drug uptake mediated cisplatin sensitivity by inhibiting the GJB2 expression. This study demonstrates that GJB2 is a potential therapeutic target for overcoming cisplatin resistance in OC by upregulating TNC expression. Epicatechin may enhance cisplatin efficacy by targeting GJB2.