Translational gastroenterology and hepatology
Fedratinib treatment correlates with suppressed STAT3/AKT/calpain-1 signaling and inhibits hepatocellular carcinoma progression
By Zhao Y, Chen S, Zhao Z and 13 others.
Abstract
Background
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death, and effective targeted therapies remain limited. Fedratinib, a clinically approved JAK2 inhibitor, has shown antitumor activity in hematologic malignancies, however, its role in HCC remains unclear. This study aimed to investigate the antitumor effects of fedratinib in HCC.
Methods
The effects of fedratinib were examined in Huh7 and Hepa1-6 HCC cells using proliferation, migration, invasion, apoptosis, and cell cycle assays. Cell-based surface plasmon resonance (SPR) was used to assess concentration-dependent whole-cell association signals between fedratinib and intact HCC cell monolayers. In vivo, Hepa1-6-Luc subcutaneous allografts were treated with intraperitoneal fedratinib. Western blotting and enzymatic assays were performed to detect STAT3, AKT, calpain-1 and Bcl-2.