163P An evaluation of the anti-cancerous potential of 5-epi- sinuleptolide in pancreatic cancer

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Background CancercausesthehighestlevelofmortalityinTaiwanamongthepatient population, pancreatic cancer being a large contributor to this circumstance. Even with advancements made in chemotherapeutic and radiation therapies, the likelihood that a patientwill survive pancreatic canceris less than a1.9 percent. 5-epi-sinuleptolide, the norditerpene extracted from Sinularia sp has shown cytotoxic effects leading to apoptosisandanti-cancerousactivity,buttheprecisemechanismsbywhichitcarries out these phenomena have yet to be deduced. The goal of this research was to investigate and reveal the mechanisms by which 5-epi-sinuleptolide inhibited cell growth, decreased cell viability, caused cell cycle arrest, and ultimately induced pancreatic cancer cell death. Methods In our study, two pancreatic cancer cell lines, Panc-1 and BxPC-3 were used, which present Gemzar-resistant and -sensitive respectively. The cell viability was determinedbyMTTassay.TheAnnexinV/PI,caspase-3activityandcellcyclewere analyzed by flow cytometry. Transwell invasion assay was applied for invasiveness measurement. The underlining mechanisms regulated by 5-epi-sinuleptolide on pancreatic cancer cells were revealed by western blotting. Results In thisstudy,theinhibitoryeffects ofcellgrowthupon5-epi-sinuleptolideon pancreaticcancercellsweredetermined.5-epi-sinuleptolidetreatmentcouldinduce apoptosis,activationofcaspase-3andcellcyclearrestinpancreaticcancercells.Besides, the invasion and cell proliferation were inhibited after 24 h treatment of 5-epi- sinuleptolide. The results of western blotting showed that 5-epi-sinuleptolide could surely inhibit STAT3, AKT and ERK phosphorylation and decrease the endogenous protein level through a transcriptional regulation-independent mechanism. Conclusions In conclusion, the diminution of the phosphorylation parallel with the decrease of the endogenous protein level of STAT3, AKT and ERK might play the role, at least partially, in the anti-pancreatic cancer potential of 5-epi-sinuleptolide. Legal entity responsible for the study Kuo Yu Hsuan Funding Chi-Mei Medical Center Research Funding: CMFHR10251 Disclosure All authors have declared no conflicts of interest.