Activation of glucagon-like peptide-1 receptor inhibits tumourigenicity and metastasis of human pancreatic cancer cells via PI3K/Akt pathway

2014 ◽  
Vol 16 (9) ◽  
pp. 850-860 ◽  
Author(s):  
H. Zhao ◽  
L. Wang ◽  
R. Wei ◽  
D. Xiu ◽  
M. Tao ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Human Pancreatic Cancer ◽  
Akt Pathway ◽  
Pancreatic Cancer Cells ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Activation of glucagon-like peptide-1 receptor inhibits growth and promotes apoptosis of human pancreatic cancer cells in a cAMP-dependent manner

2014 ◽  
Vol 306 (12) ◽  
pp. E1431-E1441 ◽  
Author(s):  
Hejun Zhao ◽  
Rui Wei ◽  
Liang Wang ◽  
Qing Tian ◽  
Ming Tao ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Human Pancreatic Cancer ◽  
Dependent Manner ◽  
Pancreatic Cancer Cells ◽  
Tumor Tissues ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1) promotes pancreatic β-cell regeneration through GLP-1 receptor (GLP-1R) activation. However, whether it promotes exocrine pancreas growth and thereby increases the risk of pancreatic cancer has been a topic of debate in recent years. Clinical data and animal studies published so far have been controversial. In the present study, we report that GLP-1R activation with liraglutide inhibited growth and promoted apoptosis in human pancreatic cancer cell lines in vitro and attenuated pancreatic tumor growth in a mouse xenograft model in vivo. These effects of liraglutide were mediated through activation of cAMP production and consequent inhibition of Akt and ERK1/2 signaling pathways in a GLP-1R-dependent manner. Moreover, we examined GLP-1R expression in human pancreatic cancer tissues and found that 43.3% of tumor tissues were GLP-1R-null. In the GLP-1R-positive tumor tissues (56.7%), the level of GLP-1R was lower compared with that in tumor-adjacent normal pancreatic tissues. Furthermore, the GLP-1R-positive tumors were significantly smaller than the GLP-1R-null tumors. Our study shows for the first time that GLP-1R activation has a cytoreductive effect on human pancreatic cancer cells in vitro and in vivo, which may help address safety concerns of GLP-1-based therapies in the context of human pancreatic cancer.

Apigenin Inhibits the GLUT-1 Glucose Transporter and the Phosphoinositide 3-Kinase/Akt Pathway in Human Pancreatic Cancer Cells

Pancreas ◽  
2008 ◽  
Vol 37 (4) ◽  
pp. 426-431 ◽  
Author(s):  
Laleh G. Melstrom ◽  
Mohammad R. Salabat ◽  
Xian-Zhong Ding ◽  
Benjamin M. Milam ◽  
Matthew Strouch ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Glucose Transporter ◽  
Human Pancreatic Cancer ◽  
Akt Pathway ◽  
Glut 1 ◽  
Pancreatic Cancer Cells ◽  
Phosphoinositide 3 Kinase

scholarly journals HUMAN PANCREATIC CANCER CELLS UNDERGO PROFOUND METABOLIC REPROGRAMMING TOWARDS CELLULAR STEMNESS AS ADAPTATION TO INHIBITION OF THE AKT PATHWAY

2020 ◽  
Author(s):  
Hugo Arasanz ◽  
Carlos Hernández ◽  
Ana Bocanegra ◽  
Luisa Chocarro ◽  
Miren Zuazo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Pancreatic Adenocarcinoma ◽  
Mitochondrial Biogenesis ◽  
Metabolic Reprogramming ◽  
Human Pancreatic Cancer ◽  
Akt Pathway ◽  
Pancreatic Cancer Cells ◽  
Cytotoxic Therapies

ABSTRACTCancer cells acquire resistance to cytotoxic therapies targeting major survival pathways by adapting their metabolism. The AKT pathway is a major regulator of human pancreatic adenocarcinoma progression. The mechanisms of adaptation to long-term silencing of AKT isoforms of pancreatic cancer cells were studied. Following silencing, cancer cells remained quiescent for long periods of time, after which they recovered proliferative capacities. Adaptation caused profound proteomic changes largely affecting mitochondrial biogenesis, energy metabolism, and acquisition of a number of distinct cancer stem cell (CSC) characteristics depending on the AKT isoform that was silenced. The adaptation to AKT1 silencing drove most de-differentiation and acquisition of stemness through C-MYC down-modulation and NANOG up-regulation, which were required for survival of adapted CSCs. The changes associated to adaptation sensitized cancer cells to inhibitors targeting regulators of oxidative respiration and mitochondrial biogenesis. In vivo pharmacological co-inhibition of AKT and mitochondrial metabolism effectively controlled pancreatic adenocarcinoma growth in pre-clinical models.

In Vitro and In Vivo Antitumor Efficacy of Docetaxel and Sorafenib Combination in Human Pancreatic Cancer Cells

2010 ◽  
Vol 999 (999) ◽  
pp. 1-11
Author(s):  
P. Ulivi ◽  
C. Arienti ◽  
W. Zoli ◽  
M. Scarsella ◽  
S. Carloni ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Antitumor Efficacy ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells

scholarly journals Cyathus striatus Extract Induces Apoptosis in Human Pancreatic Cancer Cells and Inhibits Xenograft Tumor Growth In Vivo

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2017
Author(s):  
Lital Sharvit ◽  
Rinat Bar-Shalom ◽  
Naiel Azzam ◽  
Yaniv Yechiel ◽  
Solomon Wasser ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Pancreatic Cancer Cell Line ◽  
Cancer Cell Line ◽  
Culture Liquid ◽  
Human Pancreatic Cancer ◽  
P53 Signaling ◽  
Pancreatic Cancer Cells

Pancreatic cancer is a highly lethal disease with limited options for effective therapy and the lowest survival rate of all cancer forms. Therefore, a new, effective strategy for cancer treatment is in need. Previously, we found that a culture liquid extract of Cyathus striatus (CS) has a potent antitumor activity. In the present study, we aimed to investigate the effects of Cyathus striatus extract (CSE) on the growth of pancreatic cancer cells, both in vitro and in vivo. The proliferation assay (XTT), cell cycle analysis, Annexin/PI staining and TUNEL assay confirmed the inhibition of cell growth and induction of apoptosis by CSE. A Western blot analysis demonstrated the involvement of both the extrinsic and intrinsic apoptosis pathways. In addition, a RNAseq analysis revealed the involvement of the MAPK and P53 signaling pathways and pointed toward endoplasmic reticulum stress induced apoptosis. The anticancer activity of the CSE was also demonstrated in mice harboring pancreatic cancer cell line-derived tumor xenografts when CSE was given for 5 weeks by weekly IV injections. Our findings suggest that CSE could potentially be useful as a new strategy for treating pancreatic cancer.

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