Gemcitabine, a cytotoxic nucleoside analogue, is the current clinical standard of care for advanced pancreatic cancer but has a response rate of less than 20% . To establish that ER stress induced by PA leads to apoptotic cell death, we treated pancreatic cancer cells with PA plus TUDCA. UPR is initiated by three ER transmembrane receptors: activating transcription factor-6 (ATF6), inositol-requiring enzyme 1 (IRE1) and PKR-like ER kinase (PERK) . Under these conditions, protein folding is disrupted and unfolded or misfolded proteins accumulate in the ER lumen, which lead to ER stress [8, 9]. Yang Y, Li C, Xiang X, Dai Z, Chang J, Zhang M, et al. Both systems act as quality control processes to facilitate protein folding and suppress protein synthesis [10, 11]. We are experimenting with display styles that make it easier to read articles in PMC. Data were compared by ANOVA with Bonferroni correction for the significant level. Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, et al. Klimstra DS, Heffess CS, Oertel JE, Rosai J. Acinar cell carcinoma of the pancreas. Jiang J, Slivova V, Harvey K, Valachovicova T, Sliva D. Ganoderma lucidum suppresses growth of breast cancer cells through the inhibition of Akt/NF-kappaB signaling, Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Lust S, Vanhoecke B, VANG M, Boelens J, VANM H, Kaileh M, et al. Skarda JS, Honick AB, Gibbins CS, Josselson AR, Rishi M. Papillary-cystic tumor of the pancreas in a young woman: fine-needle aspiration cytology, ultrastructure and DNA analysis. 1869-1874, 10.3892/ijo.2013.1902 PANC-1 and MIA PaCa-2 cells were exposed to different concentrations of PA for 24 h and the c-PARP was detected by western blot analysis. The mice were acclimatized for 1 week and treated with PA (0, 25 or 50 mg kg-1 of body weight, n = 15 per group) by i.p. Increasing translation of ATF4 results in the transcriptional activation of CHOP . nutrient and oxygen deprivation) and intrinsic factors (e.g. Bortezomib, a potent and selective inhibitor of proteasome, sensitizes pancreatic cancer cells to ER stress-induced apoptosis and strongly enhances the antitumor activity of cisplatin . Representative blots from three experiments were shown and quantitative data composed of all the experiments in C), G) PANC-1 and D), H) MIA PaCa-2 cells with statistical analysis were below the representative blot image. However, based on in vitro cell-based and in vivo mouse xenograft results in our study, we concluded that PA induced apoptosis of pancreatic cancer cells through activating ER stress. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Methods . 3 These seemingly contradicted results show that the activities of different triterpene acids are complicated, depending on the various structures, cell types, treatment times, concentrations and so on. Your submission has been received! ER is the principal site of protein synthesis, folding and modification . This salt combination may also be used for purposes not listed in this medication guide. CHOP, also known as DDIT3 (DNA-damage-inducible transcript 3), is involved in growth arrest and apoptosis following DNA damage and a variety of stress conditions, such as nutrient deprivation and treatment with anticancer agents . (A) PANC-1 and (B) MIA PaCa-2 cells were treated with PA (0–30 μM) for 24 h, respectively. However, if the stress cannot be resolved, signaling through ATF6, IRE1 and PERK trigger pro-apoptotic response through activation of downstream molecules, such as transcription factor C/EBP homologous protein (CHOP), which further induce apoptosis during prolonged ER stress . Poria cocos has many functions, such as anti-inflammatory and anti-tumor effects. The activated PERK kinase phosphorylates the alpha subunit of the eukaryotic initiation factor 2 (eIF2α), which results in the first step in the UPR: decreased translation initiation and protein synthesis [14, 15]. A research from Indiana University stated that a traditional remedy extracted from pine-bearing Poria Cocos, a type of medical mushrooms, can block the MMP gene. Edelfosine, an alkyl-lysophospholipid analog, induces ER stress and apoptosis in vitro and in vivo through its accumulation in the ER . The microarray studies were carried out using the facilities of the Center for Medical Genomics at Indiana University School of Medicine. Our results indicate that non-toxic dose of PA suppresses the growth of chemotherapy resistant pancreatic tumor through inducing ER stress mediated apoptosis. Those are familiar names of people who have died from pancreatic cancer. Cortex Moutan / Poria Cocos is used for Cancer, Bladder cancer, Bladder tumour, Pancreatic cancer, Inflammation, Oxidative stress, Viral infections and other conditions. *P<0.050 was considered to be significant when compared to control (n = 7) by Student t-test. Images are representative of control and PA treatment (25 mg kg-1 and 50 mg kg-1) groups. Poria cocos (Polyporaceae) is a saprophytic fungus that grows in diverse species of Pinus. Liver, spleen, kidney, lung and heart were harvested, fixed in 10% neutral-buffered formalin at 4°C for 24 h followed tissue processing overnight and then embedded in paraffin. 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