Authors: Meiying Li Xuejun Yu Hui Guo Limei Sun Aijun Wang Qiji Liu Xiuwen Wang Jisheng Li
Publish Date: 2013/11/12
Volume: 35, Issue: 3, Pages: 2461-2471
Abstract
As one of the most aggressive human malignancies pancreatic cancer is a leading cause of cancerrelated deaths worldwide and only about 4 of patients will live 5 years after diagnosis Eighty to approximately eightyfive percent of patients are diagnosed with an unresectable or metastatic disease which is correlated with poor prognosis and low survival rate Therefore it is tremendously significant to exploit novel chemicals to prevent and treat pancreatic cancer Previous research and clinical studies have demonstrated that many natural products derived from traditional Chinese medicine TCM such as camptothecin derivatives and vinca alkaloids could be effective antitumor compounds hinting that TCM is a promising source for developing new antitumor drugs In this report we investigated the effects of bufalin a primary active ingredient of the traditional Chinese medicine ChanSu on pancreatic cancer cell lines PANC1 and CFPAC1 and studied the underlying molecular mechanism We found that exposure to bufalin could suppress the proliferation of pancreatic cancer cells time and dose dependently We used flow cytometry to study the effects of bufalin on apoptosis and cell cycle distribution in PANC1 and CFPAC1 cells The results indicated that bufalin could significantly induce both apoptosis and G2/M cell cycle arrest in pancreatic cancer cells With western blotting we found that the expression level of an antiapoptotic protein heat shock protein 27 Hsp27 and its partner molecule pAkt was decreased upon the treatment with bufalin Besides bufalin activated procaspase3 and procaspase9 and modulated the expression level of Bcl2 and Bax These data suggested that bufalin may trigger apoptosis by targeting Hsp27 which could inhibit apoptosis by interfering with key apoptotic proteins The influence on the level of cylinB1 CDK1 and p21 was also observed after bufalin treatment and the relationship between Hsp27 and the cell cyclerelated proteins mentioned above deserves much more research In addition our data showed that bufalin could enhance the growth inhibition effect of gemcitabine in above pancreatic cancer cells Taken together bufalin might be worthy of further study for its potential as a therapeutic agent for pancreatic cancer treatmentThis study was supported by the National Natural Science Foundation of China 81201934 81100645 Specialized Research Fund for the Doctoral Program of Higher Education 20120131120061 China Postdoctoral Science Foundation 2013 M531612 and Independent Innovation Foundation of Shandong University 2012TS155
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