Transforming Growth Factor Beta Receptor I Inhibitor Sensitizes Drug-resistant Pancreatic Cancer Cells to Gemcitabine

Resistance to gemcitabine is a major obstacle in the treatment of advanced pancreatic cancer. Previous exploration of protein kinase inhibitors demonstrated that blocking transforming growth factor-β (TGFβ) signal enhances the efficacy of gemcitabine in pancreatic cancer cells. We analyzed the cell viability after combinational treatment of TGFβ receptor I (TβRI) inhibitors, SB431542 and SB525334 with gemcitabine in pancreatic cancer cells. In addition, apoptotic cell death and cell migration were measured. Combination with TβRI inhibitors significantly augmented the cytotoxicity of gemcitabine in both parental and gemcitabine resistant pancreatic cancer cells. SB525334 significantly increased apoptotic cell death in gemcitabine-resistant cells. Treatment of SB525334 also affected the AKT signalling pathway, which plays a crucial role in gemcitabine resistance. Migration assay also revealed that blocking TβRI reduces cell migration. Chemotherapeutic approaches using SB525334 might enhance the treatment benefit of the gemcitabine-containing regimens in the treatment of pancreatic cancer patients.