| Summary: | 碩士 === 國立交通大學 === 生物科技學系 === 105 === Pancreatic cancer is one of the most malignant cancers. The incident rate of pancreatic cancer is eleventh, but the cancer death is eighth in all cancers worldwide. Furthermore, the incidence is gradually elevated especially in developed countries. In Taiwan, it becomes the eighth leading causes of cancer death from twelfth in the past twenty years. The high propensity of invasion and metastasis leads to the worst outcome. The five-year survival rate of pancreatic cancer is only 5%. Despite the strong resistance to chemotherapy and radiotherapy of pancreatic cancer, gemcitabine is still considered as the standard therapeutic option since 1997. To improve the treatment, gemcitabine and 5-fu based combination therapy have been proposed. Four of the combination regimens can significantly prolong the survival of the patients. However, the efficacy is still finite and the excessive adverse effect can not be ignored. Hence, a novel therapeutic agent is urgently needed.
Paeonol, a major ingredient of traditional Chinese medicinal herb Cortex moutan, has been found that exert anti-cancer efficacy, but it has a poor bioavailability. In the current study, we synthesized novel paeonol derivatives in order to identify a more effective anti-pancreatic cancer agent. To evaluate the anti-pancreatic cancer efficacy of these derivatives, two pancreatic cancer cell lines, PANC-1 and BxPC-3, were applied. Among these derivatives, we found that 3k2 and 3l1 posted significant cytotoxic effect to human pancreatic cancer cells. Both of them can induce apoptosis and cell cycle arrest. Our study revealed that 3k2 and 3l1 treatments inhibit the anti-apoptotic gene XIAP expression. Furthermore, 3k2 and 3l1 also downregulated the phosphorylation of Akt and ERK1/2. These results suggest that paeonol derivatives 3k2 and 3l1 might be potential therapeutic agents for the treatment of pancreatic cancer.
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