Sorafenib alleviates inflammatory signaling of tumor microenvironment in lung cancer

Abstract:Background: This study was designed to assess the possible beneficial effects of sorafenib (SOR) in diethylnitrosamine (DEN) induced lung carcinogenesis in male rats and also to examine its probable mechanisms of action. Methods and results: A total of 30 adult male rats were divided into three groups as (1) control, (2) DEN, and (3) DEN+SOR. The chemical induction of lung carcinogenesis was performed by injection of DEN intraperitoneally at 150 mg/kg once a week for two weeks. The DEN-administered rats were co-treated with SOR of 10 mg/kg by oral gavage for 42 alternate days. Serum samples were analyzed to determine SOX2 levels. Levels of SOX2, TNF-α and IL-1β were measured in lung tissue supernatants. Lung sections were evaluated histopathologically. Also, COX-2 and JNK were analyzed by immunohistochemistry and immunofluorescence methods respectively. SOR reduced the level of SOX2 that maintenance of cancer stemness and tumorigenicity, and TNF-α and IL-1β levels. Furthermore, SOR reduced lung histopathological structure and suppressed COX-2 and JNK expressionConclusions: These results suggest that SOR reduces inflammation in the tumor microenvironment and decreases the level of SOX2 which has an important role in maintaining cancer stem cell properties.