BH3 Mimetic ABT-199 Enhances the Sensitivity of Gemcitabine in Pancreatic Cancer in vitro and in vivo

Digestive Diseases and Sciences
Yi ZhouShuncai Zhang

Abstract

Pancreatic cancer is an aggressive malignancy with poor prognosis. Gemcitabine is the standard chemotherapeutic drug used to treat the disease; however, it has a low response rate. Therefore, there is an urgent need to develop new and safe therapies to enhance sensitivity to gemcitabine in treating pancreatic cancer. The synergistic effect of gemcitabine combined with specific B cell CLL/lymphoma 2 (Bcl-2) inhibitor ABT-199 against pancreatic cancer was tested using cell viability, cell cycle, and apoptosis assays in vitro and in an MIA Paca-2 xenograft model in vivo. Its underlying mechanism was explored using western blotting analysis of Bcl-2 family proteins. ABT-199 not only enhanced the effect of gemcitabine on cell growth inhibition but also promoted gemcitabine-induced apoptosis in pancreatic cancer cell lines. Gemcitabine decreased the expression of anti-apoptotic protein Mcl-1 but increased the expression of anti-apoptotic protein Bcl-2. ABT-199 downregulated the gemcitabine-induced production of Bcl-2 and increased the expression of pro-apoptotic protein Bcl-2 interacting protein (BIM). Mouse xenograft experiments also confirmed the synergistic effect of gemcitabine and ABT-199 on tumor growth inhibition and the induc...Continue Reading

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Citations

Dec 14, 2018·International Journal of Molecular Sciences·Marilina García-ArandaMaximino Redondo
Jun 26, 2021·The International Journal of Biochemistry & Cell Biology·Yeliz AkaOzgur Kutuk
Nov 4, 2021·Expert Opinion on Investigational Drugs·Byung Woog Kang, Ian Chau

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