Knocking down CLDN7 enhanced the effect of cisplatin in OC cells by regulating mitophagy

Ovarian cancer (OC) remains a leading cause of female mortality due to its complex pathological progression and the lack of early screening methods. The cisplatin chemotherapy resistance is a stumbling block in the treatment of ovarian cancer. Aberrant expression of Claudins (CLDNs) has been implicated in several cancers including OC, especially CLDN7, while the vital roles of CLDN7 in OC and cisplatin chemoresistance remain unclear. Methods ONCOMINE, GEPIA, the Human Protein Atlas, cBioPortal databases, CCK-8 assay, RT-PCR, Western Blot, transwell assay, Immunofluorescence (IF), rescue experiment and in vivo xenograft experiments, were utilized in this study.

Our research found that CLDN7 is preferentially enriched on the cytoplasmic membrane of SKOV3 cells. The expression level of CLDN7 was elevated in ovarian cancer, indicating its association with the occurrence of ovarian cancer. We discovered that CLDN7 was significantly increased in SKOV3/DDP cells, with enhanced autophagy and mitophagy levels. To further explore the possible mechanism of CLDN7 in cisplatin resistance, we knocked down CLDN7 in SKOV3/DDP cells and found that autophagy and mitophagy related proteins decreased, suggesting that CLDN7 maybe involved in cisplatin resistance by regulating autophagy and mitophagy. Colocalization of LC3 with mitochondria (MitoTracker) by immunofluorescence provides direct evidence of mitophagy. The migration and invasion ability of SKOV3/DDP cells decreased when CLDN7 was knocked down. The xenograft models experiment results indicated that silencing CLDN7 could enhance the inhibitory effect of cisplatin on tumor growth.

Knocking down CLDN7 enhanced the effect of cisplatin in OC cells by regulating mitophagy.This provides a theoretical basis for cisplatin resistance in future studies in OC.