Study of the enhanced anticancer efficacy of gambogic acid on Capan-1 pancreatic cancer cells when mediated via magnetic Fe3O4 nanoparticles

Abstract

Cailian Wang1,*, Haijun Zhang1,*, Baoan Chen2, Haitao Yin1, Wenwen Wang11Department of Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing, People's Republic of China; 2Department of Hematology, Zhongda Hospital, Medical School, Southeast University, Nanjing, People's Republic of China *These authors contributed equally to this workBackground: Gambogic acid (GA), a potent anticancer agent, is limited in clinical administration due to its poor water solubility. The aim of this study was to explore a drug delivery system based on magnetic Fe3O4 nanoparticles (MNP- Fe3O4) conjugated with GA to increase water solubility of the drug and enhance its chemotherapeutic efficiency for pancreatic cancer.Methods: GA was conjugated with the MNP- Fe3O4 colloidal suspension by mechanical absorption polymerization to construct GA-loaded MNP- Fe3O4, which acted as a drug delivery system.Results: Combination therapy with GA and MNP- Fe3O4 induced remarkable improvement in anticancer activity, which was demonstrated by optical microscopic observations, MTT assay, and nuclear DAPI staining. Furthermore, the possible signaling pathway was explored by Western blot. In Capan-1 pancreatic cancer cells, our observations demonstrated that this strategy could enhance potential anticancer efficiency by inducing apoptosis. The mechanisms of the synergistic effect may be due to reducing protein expression of Bcl-2 and enhancing that of Bax, caspase 9, and caspase 3.Conclusion: These findings demonstrate that a combination of GA and MNPs- Fe3O4 represents a promising approach to the treatment of pancreatic cancer.Keywords: gambogic acid, pancreatic cancer, magnetic nanoparticles, drug delivery system, apoptosis