The Activity Study of Pancreatic Cancer Inhibited by Guttiferone K both in vitro and in vivo / 世界科学技术-中医药现代化

ABSTRACT

This study aimed at exploring the effects of Guttiferone K (GUTK),a compound isolated from G.yunnanensis,on inhibiting the proliferation of pancreatic cancer cells both in vitro and in vivo.MTT assay was used to detect the inhibitory effects of GUTK on the proliferation of five human pancreatic cancer cell lines.Western blot was adopted to detect the apoptosis-related protein expressions of Caspase-3,poly adenosinediphosphate-ribose polymerase (PARP) and Bcl-xL.For in vivo study,the human pancreatic cancer cell MIA PaCa-2 was orthotopically injected into the pancreatic tail of the orthotopic mice.One week later,GUTK was administered by intraperitoneal (i.p.) injection every other day for 4 weeks.The volume and weight of the tumor tissue were measured.The protein expression level of cleaved caspase-3 in tumor tissue of all the groups was quantified by immunohistochemistry.As a result,it was found that GUTK effectively inhibited the proliferation of the five human pancreatic cancer cell lines at a low concentration.GUTK induced caspase-related apoptosis by triggering a series of events in MIA PaCa-2 cells including cleaved Caspase-3 and PARP activation,Bcl-xL down-regulation,and eventually cell death in a time and dose dependent manner.Furthermore,in vivo study revealed that intraperitoneal injection of GUTK significantly suppressed the growth of pancreatic cancer cells in the orthotopic mouse models,and the protein level of cleaved caspase-3 was increased in the GUTK and gemcitabine treated groups.It was concluded that GUTK induced apoptosis in human pancreatic cancer both in vitro and in vivo,and was potential to develop into a clinical anticancer agent.