Transforming growth factor beta receptor I inhibitor sensitizes drug-resistant pancreatic cancer cells to gemcitabine.

Abstract

BACKGROUND:

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.

MATERIALS AND METHODS:

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.

RESULTS:

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.

CONCLUSION:

Chemotherapeutic approaches using SB525334 might enhance the treatment benefit of the gemcitabine-containing regimens in the treatment of pancreatic cancer patients.

• Authors: Yeon Jeong Kim, Jae Seok Hwang, Young Bin Hong, Insoo Bae, Yeon-Sun Seong
• Journal: Anticancer research (Anticancer Res) Vol. 32 Issue 3 Pg. 799-806 (Mar 2012) ISSN: 1791-7530 [Electronic] Greece
• PMID: 22399597 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 6-(2-tert-butyl-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline
• Antimetabolites, Antineoplastic
• Imidazoles
• Quinoxalines
• Receptors, Transforming Growth Factor beta
• Deoxycytidine
• Protein Serine-Threonine Kinases
• Receptor, Transforming Growth Factor-beta Type I
• Gemcitabine

Topics

• Antimetabolites, Antineoplastic
• Cell Line, Tumor
• Deoxycytidine (analogs & derivatives, pharmacology)
• Humans
• Imidazoles (pharmacology)
• Pancreatic Neoplasms (pathology)
• Protein Serine-Threonine Kinases (antagonists & inhibitors)
• Quinoxalines (pharmacology)
• Receptor, Transforming Growth Factor-beta Type I
• Receptors, Transforming Growth Factor beta (antagonists & inhibitors)
• Gemcitabine