Inhibition of Apoc1 reverses resistance of sorafenib by promoting ferroptosis in esophageal cancers.

Drug resistance is an obstacle in therapy of esophageal cancers (ECs), and the role of ferroptosis in progression ECs is still not clearly clarified. In the present study, we investigated the role of Apolipoprotein C1 (Apoc1) in regulating the sorafenib resistance in EC cells. Apoc1 was knock down after infection with Apoc1 shRNA lentivirus and stable cell lines for Apoc1 knockdown were screened. Cell viabilities were tested by MTT assay. ROS, MDA, and GSH tested by specific kits. In vivo experiment in nude mice were performed to test the correlation of Apoc1 and ferroptosis. The expression of Apoc1 and GPX4 was tested by western blotting. The results showed that Apoc1 was highly expressed in EC tissues and associated with poor overall survival rate of EC. Knockdown Apoc1 overcame resistance of sorafenib in EC cells and promoted erastin and sorafenib induced ferroptosis by upregulating the levels of ROS and MDA and downregulating the level of GSH in OE19/Sora and EC109/Sora cells. Rescue experiments proved that Apoc1 regulated sorafenib induced ferroptosis via GPX4. Furthermore, knockdown of Apoc1 inhibited the tumor progression by promoting ferroptosis in nude mice. In conclusion, knockdown Apoc1 overcome resistance of sorafenib in EC cells and in vivo by promoting sorafenib induced ferroptosis via GPX4. Targeting Apoc1 might be an effective way to reverse the drug resistance of sorafenib via inducing ferroptosis in EC progression.