Investigations of the effectiveness of a novel multiple kinase inhibitor BPR1K-X in targeting human pancreatic cancer cells

  • 黃 義純

Student thesis: Master's Thesis


Pancreatic cancer is widely known as the most aggressive solid malignancies with poor prognosis The overall 5-year survival is 6% and the standard treatment with gemcitabine only yields a median survival of 5 6 months in advanced disease Therefore developing novel therapeutic approaches is desperately needed Previous studies have shown that overexpression of oncogenic Aurora kinases play a critical role in pancreatic carcinogenesis Aberrant mTOR signaling in cancer cells is also associated with the drug resistance and tumorigenic potential Besides recent studies reveal that TrkA plays an important role in pancreatic cancer development making these signaling pathways as important anticancer targets In this study we aim to elucidate the anticancer activity of a novel multiple kinase inhibitor BPR1K-X in human pancreatic cancer cell lines In vitro kinase inhibition assay indicated that BPR1K-X inhibited multiple kinase activity such as Aurora A and B and TrkA at low nano-molar concentrations Results of the MTT cell viability assay BrdU cell proliferation assay and LDH cytotoxicity assay showed that BPR1K-X was effective in targeting the human AsPC-1 MIA PaCa-2 BxPC-3 and PANC-1 pancreatic cancer cells in vitro At the molecular level Western blot analysis revealed that BPR1K-X suppressed p-Aurora A and B p-mTOR and p-TrkA expression in pancreatic cancer cells In addition Western blot analysis and flow cytometric analysis revealed that BPR1K-X decreased the expression of cyclin B1 and induced endo-reduplication by the formation of polyploidy respectively It also modulated autophagy and induced apoptosis in the treated pancreatic cancer cells Taken together our study suggests that BPR1K-X is a potent multiple kinase inhibitor that is able to target human pancreatic cancer cells
Date of Award2014 Jul 26
Original languageEnglish
SupervisorChun Hei Antonio Cheung (Supervisor)

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