scholarly journals Activation of GLP-1 receptor enhances the chemosensitivity of pancreatic cancer cells

2020 ◽  
Vol 64 (2) ◽  
pp. 103-113
Author(s):  
He-jun Zhao ◽  
Xia Jiang ◽  
Li-juan Hu ◽  
Lei Yang ◽  
Lian-dong Deng ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Pancreatic Cancer Cell ◽  
Pancreatic Cancer Cell Line ◽  
Cancer Cell Line ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells

This study aimed to determine whether and how the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide affects the chemoresistance and chemosensitivity of pancreatic cancer cells to gemcitabine in vitro and in vivo. The GLP-1R and protein kinase A (PKA) levels were compared between the human pancreatic cancer cell line PANC-1 and the gemcitabine-resistant cell line PANC-GR. The in vitro effects of liraglutide on the cell proliferation and apoptosis as well as the nuclear factor-kappa B NF-κB expression levels of PANC-GR cells were evaluated. In addition, a mouse xenograft model of human pancreatic cancer was established by s.c. injection of PANC-1 cells, and the effects of liraglutide on the chemosensitivity were evaluated in vitro and in vivo. In contrast to PANC-1 cells, PANC-GR cells exhibited lower expression levels of GLP-1R and PKA. Incubation with liraglutide dose dependently inhibited the growth, promoted the apoptosis, and increased the expression of GLP-1R and PKA of PANC-GR cells. Similar effects of liraglutide were observed in another human pancreatic cancer cell line MiaPaCa-2/MiaPaCa-2-GR. Either the GLP-1R antagonist Ex-9, the PKA inhibitor H89, or the NF-κB activator lipopolysaccharide (LPS) could abolish the antiproliferative and proapoptotic activities of liraglutide. Additionally, each of these agents could reverse the expression of NF-κB and ABCG2, which was decreased by liraglutide treatment. Furthermore, liraglutide treatment increased the chemosensitivity of pancreatic cancer cells to gemcitabine, as evidenced by in vitro and in vivo experiments. Thus, GLP-1R agonists are safe and beneficial for patients complicated with pancreatic cancer and diabetes, especially for gemcitabine-resistant pancreatic cancer.

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.

scholarly journals Synergistic Effect of the Combination of Polyphenols with Gemcitabineon Pancreatic Cancer Cell line AsPC-1

2017 ◽  
Vol 2 (1) ◽  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Line ◽  
Efflux Pump ◽  
Flow Cytometric Analysis ◽  
Pancreatic Cancer Cell Line ◽  
Cancer Cell Line ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cell ◽  
Pancreatic Cancer Cells

In our diet, polyphenols are micronutrients with an important role in the prevention of degenerative diseases such as cancer and cardiovascular diseases. Particularly, Pancreatic cancer is one of the most aggressive cancers, with only about 5% of patients surviving 5 years past the initial diagnosis. Despite advances with current chemotherapy combinations, overall survival outcomes are still require novel therapeutic approaches. Here, we examined the efficacy of combined treatments of polyphenols and gemcitabine the standard of treatment for patients with metastatic pancreatic cancer in human pancreatic cancer cells. For that purpose, the pro-apoptic effects of gemcitabine were studied on the human pancreatic cell line AsPC1 in presence or absence of several polyphenols, in order to evaluate if they latter are able to potentialize gemcitabine cytotoxicity. Our study aims to investigate the implication of MDR1 (multidrug transporter)in resistance to gemcitabine and if the studied polyphenol could target this drug efflux pump in AsPC-1 cells by flow cytometric analysis. We observed that 5µg/ml gemcitabine in combination with 15 µg/ml of selected polyphenol (Catechin, Quercetin, Bergamottin, Rhamnetin) was more effective than gemcitabine alone, by increased in the percentage of dead cells up to 60%. Morever our results demonstrated that some polyphenols (Quercetin) inhibit the efflux activity of MDR1. Our study in vitro suggests therefore that chemotherapy with gemcitabine might be significantly increased upon combination with specific polyphenol. In conclusion, polyphenols may be promising agents for novel combination therapy since they potentialize the cytotoxic activity of gemcitabine to eradicate pancreatic cancer and therefore the cellular resistance.

scholarly journals Synergistic Anticancer Effects of Gemcitabine with Pitavastatin on Pancreatic Cancer Cell Line MIA PaCa-2 in vitro and in vivo

2020 ◽  
Vol Volume 12 ◽  
pp. 4645-4665 ◽  
Author(s):  
Ya-Hui Chen ◽  
Yi-Chun Chen ◽  
Chi-Chen Lin ◽  
Yao-Peng Hsieh ◽  
Chien-Sheng Hsu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Pancreatic Cancer Cell Line ◽  
Cancer Cell Line ◽  
Anticancer Effects

scholarly journals MicroRNA Expression Profiling of Pancreatic Cancer Cell Line L3.6p1 Following B7-H4 Knockdown

2017 ◽  
Vol 44 (2) ◽  
pp. 494-504 ◽  
Author(s):  
Yun Qian ◽  
Limin Feng ◽  
Weigen Wu ◽  
Tianhao Weng ◽  
Chenyu Hu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Signaling Pathway ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Pancreatic Cancer Cell Line ◽  
Cancer Cell Line ◽  
Tumor Immune Escape ◽  
Pancreatic Cancer Cells

Background/Aims: Co-stimulating molecule B7-H4 regulates T cell-mediated immune responses, participates in tumor immune escape, and promotes the proliferation and metastasis of pancreatic cancer cells. However, the specific mechanisms are unclear. MicroRNAs (miRNAs) participated in the pathogenesis and progression of cancer. Methods: In this study, a microarray technique was used to screen B7-H4-related differentially expressed miRNAs in a pancreatic cancer cell line find those associated with pancreatic cancer. Using a miRCURYTM LNA Array approach, we compared the miRNA expression profiles of L3.6p1 pancreatic cancer cells transfected with B7-H4 siRNA for 72 h with those transfected with non-target siRNAs. Results: B7-H4 siRNA significantly up-regulated 57 miRNAs and down-regulated 14 miRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis of predicted miRNA targets showed that these genes were mainly involved in protein binding, pathways in cancer, mitogen-activated protein kinase (MAPK) signaling pathway, and phosphatidylinositol 3-kinase-Akt (PI3K-Akt) signaling pathway. Conclusions: This is the first description of target genes of B7-H4, showing that miRNAs participate in the B7-H4 mediated regulation of oncogenicity and pathogenesis of pancreatic cancer. These results may help us better understand the role of B7-H4 in the progression of pancreatic cancer and its possible mechanisms. We also provide novel biomarkers for potential treatments of pancreatic cancer.

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