| Summary: | 碩士 === 長庚大學 === 傳統中國醫學研究所 === 95 === Pancreatic cancer, with increasing incidence, is one of the most lethal cancers with an overall 5-year survival rate less than 5%. Even localized and potentially resectable disease remains poor prognosis due to the aggressive local invasion and metastasis of the tumor. Chemotherapeutic agents remain the standard of care, especially the nucleoside analogue gemcitabine, but only marginal advantage in survival and quality of life was noted. Clearly, searching novel and more effective agents against pancreatic cancer is an urgent need.
Several studies have indicated that plumbagin has anticancer and antiproliferation capacity in vitro as well as in vivo. However, its inhibitory effect on pancreatic cancer has not been explored. In this study, we investigated the effect of plumbagin on growth of human pancreatic carcinoma cell lines and the possible molecular mechanism.
Plumbagin treatment exerted a dose-dependent and time-dependent growth inhibitory effect on Panc-1 and Bxpc-3 cells. Cells treated by plumbagin had morphological changes resembling apoptosis by using Liu’s stain. Quantitative studies for apoptosis show that both the proportion of sub-G1 and Annexin V(+)/propidium iodide (-) Panc-1 cells increased after treatment with plumbagin. Plumbagin exposure caused the rapid reduction of mitochondria membrane potential, induced cytochrome c expression in the cytosol, activated caspase-9 as well as caspase-3/7, and cleaved poly ADP-ribose polymerase. Activation of caspase-8 was not evident by fluorometric and immunoblotting assay. Up-regulation of Bax, but not Bcl-2 or Bid was found after plumbagin treatment. Taken together, the results of our study suggest that plumbagin induces apoptosis in human pancreatic cancer cells through the mitochondria-mediated pathway. It implicates that plumbagin has potential for development of a novel therapeutic agent against pancreatic cancer.
|
|---|
