scholarly journals TFCP2 Overcomes Senescence by Cooperating With SREBP2 to Activate Cholesterol Synthesis in Pancreatic Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Dexiang Zhang ◽  
Pinxiang Lu ◽  
Kaihua Zhu ◽  
Haixia Wu ◽  
Yuedi Dai
Keyword(s):  
Pancreatic Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Kras Mutation ◽  
Cholesterol Synthesis ◽  
Pancreatic Cancer Cell ◽  
Regulatory Element ◽  
Cell Senescence ◽  
Pancreatic Cancer Cells

KRAS mutation is very common in pancreatic cancer. How pancreatic cancer cells overcome oncogene-induced senescence is not fully understood. Our previous studies showed that up-regulation of TFCP2 (transcription factor CP2) in pancreatic cancer promoted the growth and metastasis of pancreatic cancer cells. However, whether TFCP2 plays an important role in pancreatic cancer cell senescence is not clear. In this study, we found upregulation of TFCP2 expression in pancreatic cancer was associated with KRAS mutation. Overexpression of TFCP2 inhibited cell senescence. Knockdown of TFCP2 promoted cell senescence. Mechanistically, the interaction between TFCP2 and SREBP2 (sterol regulatory element binding transcription factor 2) synergistically activated the expression of HMGCR, a rate-limiting enzyme in cholesterol synthesis, and statins could reverse the inhibitory effect of TFCP2 on senescence. In conclusion, our study reveals a new mechanism underlying the TFCP2 regulation of pancreatic cancer cell senescence, providing a new target for the treatment of pancreatic cancer.

scholarly journals Blocking IL-6/GP130 Signaling Inhibits Cell Viability/Proliferation, Glycolysis, and Colony Forming Activity in Human Pancreatic Cancer Cells

2019 ◽  
Vol 19 (5) ◽  
pp. 417-427 ◽  
Author(s):  
Xiang Chen ◽  
Jilai Tian ◽  
Gloria H. Su ◽  
Jiayuh Lin
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Human Pancreatic Cancer ◽  
Multiple Cancer ◽  
Pancreatic Cancer Cells ◽  
Stat3 Phosphorylation

Background:Elevated production of the pro-inflammatory cytokine interleukin-6 (IL-6) and dysfunction of IL-6 signaling promotes tumorigenesis and are associated with poor survival outcomes in multiple cancer types. Recent studies showed that the IL-6/GP130/STAT3 signaling pathway plays a pivotal role in pancreatic cancer development and maintenance.Objective:We aim to develop effective treatments through inhibition of IL-6/GP130 signaling in pancreatic cancer.Methods:The effects on cell viability and cell proliferation were measured by MTT and BrdU assays, respectively. The effects on glycolysis was determined by cell-based assays to measure lactate levels. Protein expression changes were evaluated by western blotting and immunoprecipitation. siRNA transfection was used to knock down estrogen receptor α gene expression. Colony forming ability was determined by colony forming cell assay.Results:We demonstrated that IL-6 can induce pancreatic cancer cell viability/proliferation and glycolysis. We also showed that a repurposing FDA-approved drug bazedoxifene could inhibit the IL-6/IL-6R/GP130 complexes. Bazedoxifene also inhibited JAK1 binding to IL-6/IL-6R/GP130 complexes and STAT3 phosphorylation. In addition, bazedoxifene impeded IL-6 mediated cell viability/ proliferation and glycolysis in pancreatic cancer cells. Consistently, other IL-6/GP130 inhibitors SC144 and evista showed similar inhibition of IL-6 stimulated cell viability, cell proliferation and glycolysis. Furthermore, all three IL-6/GP130 inhibitors reduced the colony forming ability in pancreatic cancer cells.Conclusion:Our findings demonstrated that IL-6 stimulates pancreatic cancer cell proliferation, survival and glycolysis, and supported persistent IL-6 signaling is a viable therapeutic target for pancreatic cancer using IL-6/GP130 inhibitors.

Identification and characterization of CCK-B/gastrin receptors in human pancreatic cancer cell lines

1994 ◽  
Vol 266 (1) ◽  
pp. R277-R283 ◽  
Author(s):  
J. P. Smith ◽  
G. Liu ◽  
V. Soundararajan ◽  
P. J. McLaughlin ◽  
I. S. Zagon
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Pancreatic Cancer ◽  
Human Pancreatic Cancer Cell ◽  
Pancreatic Cancer Cells

The gastrointestinal peptide cholecystokinin (CCK) is known to stimulate growth of human pancreatic cancer in a receptor-mediated fashion. The purpose of this study was to characterize the receptor responsible for the trophic effects of CCK in cancer cells. With the use of homogenates of PANC-1 human pancreatic cancer cells grown in vitro, the binding characteristics and optimal conditions of radiolabeled selective CCK-receptor antagonists ([3H]L-365,260 and [3H]L-364,718) were examined. Specific and saturable binding was detected with [3H]L-365,260, and Scatchard analysis revealed that the data were consistent for a single site of binding with a binding affinity of 4.3 +/- 0.6 nM and a binding capacity (Bmax) of 283 +/- 68 fmol/mg protein in log phase cells. Binding was dependent on protein concentration, time, temperature, and pH and was sensitive to Na+, K+, Mg2+, and ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. In contrast to log phase cells, Bmax decreased by 80 and 92% in confluent and postconfluent cultures, respectively. Subcellular fractionation studies revealed that binding was in the membrane fraction. Competition experiments indicated that L-365,260 and gastrin were more effective at displacing the radiolabeled L-365,260 than CCK. No binding was detected with the CCK-A antagonist [3H]L-364,718. Assays performed with [3H]L-365,260 on five additional human pancreatic cancer cell lines in vitro and tumor tissue from xenografts in nude mice also revealed specific and saturable binding. These results provide the first identification of a CCK-B/gastrin receptor in human pancreatic cancer cells and tumors and explain the effects of CCK on the growth of this malignancy.

Pancreatic Cancer Cells Invasiveness is Mainly Affected by Interleukin-1β not by Transforming Growth Factor-β1

2005 ◽  
Vol 20 (4) ◽  
pp. 235-241 ◽  
Author(s):  
E. Greco ◽  
D. Basso ◽  
P. Fogar ◽  
S. Mazza ◽  
F. Navaglia ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Extracellular Matrix ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Matrigel Invasion ◽  
Matrix Adhesion ◽  
Pancreatic Cancer Cells ◽  
Tgf Β1

Background We investigated in vitro whether IL-1β and TGF-β1 affect pancreatic cancer cell growth, adhesion to the extracellular matrix and Matrigel invasion. Materials and methods Adhesion to fibronectin, laminin and type I collagen, and Matrigel invasion after stimulation with saline, IL-1β and TGF-β1 were evaluated using three primary and three metastatic pancreatic cancer cell lines. Results Extracellular matrix adhesion of control cells varied independently of the metastatic characteristics of the studied cell lines, whereas Matrigel invasion of control cells was partly correlated with the in vivo metastatic potential. IL-1β did not influence extracellular matrix adhesion, whereas it significantly enhanced the invasiveness of three of the six cell lines. TGF-β1 affected the adhesion of one cell line, and exerted contrasting effects on Matrigel invasion of different cell lines. Conclusions IL-1β enhances the invasive capacity of pancreatic cancer cells, whereas TGF-β1 has paradoxical effects on pancreatic cancer cells; this makes it difficult to interfere with TGF-β1 signaling in pancreatic cancer treatment.

scholarly journals Propofol Mediates Pancreatic Cancer Cell Activity Through the Repression of ADAM8 via SP1

2021 ◽  
Author(s):  
Yutong Gao ◽  
Yu Zhou ◽  
Chunlin Wang ◽  
Klarke Sample ◽  
Xiangdi Yu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cell Activity ◽  
Pancreatic Cancer Cell Line ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Physical Interaction ◽  
Pancreatic Cancer Cells

Abstract Background Propofol is a commonly used anesthetic with controversial effects on cancer cells. A growing number of studies have demonstrated that low concentrations of propofol are associated with tumor suppression and when used as an intravenous anesthesia improved recurrence-free survival rates for many cancers, but deeper insights into its underlying mechanism are needed. Methods The study detailed herein focuses upon the effect of propofol on pancreatic cancer cells and the mechanism by which propofol reduces ADAM8 expression. The ability of propofol to impact the proliferation, migration and cell cycle of a pancreatic cancer cell line was assessed in vitro. This was mechanistically explored following the identification of SP1 binding sites within ADAM8, which enabled the regulatory effects of SP1 on ADAM8 following propofol treatment to be further explored. Results This study was able to show that propofol significantly inhibited the proliferation, migration and invasion of pancreatic cancer cells and decreased the percentage of cells in S-phase. Propofol treatment was also shown to repress ADAM8 and SP1 expression, but was unable to affect ADAM8 expression following knockdown of SP1. Moreover, a direct physical interaction between SP1 and ADAM8 was verified using Co-immunoprecipitation and dual-luciferase reporter assays. Conclusion These results suggest that propofol represses pathological biological behaviors associated with pancreatic cancer cells through the suppression of SP1, which in turn results in lower ADAM8 mRNA expression and protein levels.

scholarly journals Fusobacterium nucleatum infection induces pancreatic cancer cell proliferation and migration through regulation of host cytokine signaling

2021 ◽  
Author(s):  
Barath Udayasuryan ◽  
Tam T.D. Nguyen ◽  
Ariana Umana ◽  
LaDeidra Monet Roberts ◽  
Raffae A Ahmad ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Pancreatic Tumor ◽  
Pancreatic Cancer Cell ◽  
Fusobacterium Nucleatum ◽  
Cellular Migration ◽  
Gm Csf ◽  
Pancreatic Cancer Cells

Pancreatic ductal adenocarcinoma (PDAC) harbors a complex tumor microbiome that has been implicated in cancer progression and resistance to chemotherapy. Recent clinical investigations uncovered a correlation between high loads of intratumor Fusobacterium nucleatum and decreased patient survival. Here we show that pancreatic cancer cell lines harboring intracellular F. nucleatum secrete elevated levels of cancer-associated cytokines including IL-8, CXCL1, GM-CSF, and MIP-3α. We report that GM-CSF directly increases the proliferation of pancreatic cancer cells, and contributes to increased cellular migration, notably in the absence of immune cell participation. This study is the first to investigate the direct impact of F. nucleatum infection on pancreatic cancer cells. Our results suggest that F. nucleatum within the pancreatic tumor microenvironment elicits infection-specific cytokine secretion that directly contributes adversely to cancer progression and warrants further research into therapeutic manipulation of the pancreatic tumor microbiome.

scholarly journals S100A6 binds to annexin 2 in pancreatic cancer cells and promotes pancreatic cancer cell motility

2009 ◽  
Vol 101 (7) ◽  
pp. 1145-1154 ◽  
Author(s):  
T Nedjadi ◽  
N Kitteringham ◽  
F Campbell ◽  
R E Jenkins ◽  
B K Park ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Motility ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Motility ◽  
Pancreatic Cancer Cells ◽  
Annexin 2

scholarly journals Chlorophyll-Mediated Changes in the Redox Status of Pancreatic Cancer Cells Are Associated with Its Anticancer Effects

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Kateřina Vaňková ◽  
Ivana Marková ◽  
Jana Jašprová ◽  
Aleš Dvořák ◽  
Iva Subhanová ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Antioxidant Properties ◽  
Redox Status ◽  
Bile Pigment ◽  
Dependent Manner ◽  
Pancreatic Cancer Cells ◽  
Anticancer Effects

Nutritional factors which exhibit antioxidant properties, such as those contained in green plants, may be protective against cancer. Chlorophyll and other tetrapyrrolic compounds which are structurally related to heme and bilirubin (a bile pigment with antioxidant activity) are among those molecules which are purportedly responsible for these effects. Therefore, the aim of our study was to assess both the antiproliferative and antioxidative effects of chlorophylls (chlorophylla/b, chlorophyllin, and pheophytina) in experimental pancreatic cancer. Chlorophylls have been shown to produce antiproliferative effects in pancreatic cancer cell lines (PaTu-8902, MiaPaCa-2, and BxPC-3) in a dose-dependent manner (10–125 μmol/L). Chlorophylls also have been observed to inhibit heme oxygenase (HMOX) mRNA expression and HMOX enzymatic activity, substantially affecting the redox environment of pancreatic cancer cells, including the production of mitochondrial/whole-cell reactive oxygen species, and alter the ratio of reduced-to-oxidized glutathione. Importantly, chlorophyll-mediated suppression of pancreatic cancer cell viability has been replicated inin vivoexperiments, where the administration of chlorophyllaresulted in the significant reduction of pancreatic tumor size in xenotransplanted nude mice. In conclusion, this data suggests that chlorophyll-mediated changes on the redox status of pancreatic cancer cells might be responsible for their antiproliferative and anticancer effects and thus contribute to the decreased incidence of cancer among individuals who consume green vegetables.

scholarly journals Novel Compound C150 Inhibits Pancreatic Cancer Cell Epithelial-to-Mesenchymal Transition and Tumor Growth in Mice

2021 ◽  
Vol 11 ◽  
Author(s):  
Tao Wang ◽  
Ping Chen ◽  
Ruochen Dong ◽  
Scott Weir ◽  
Michael Baltezor ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Epithelial To Mesenchymal Transition ◽  
Pancreatic Cancer Cell ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Pancreatic Cancer Cells

Pancreatic cancer cell epithelial-to-mesenchymal transition (EMT) is an important contributor to cell invasion and tumor progression. Therefore, targeting EMT may be beneficial for pancreatic cancer treatment. The aim of the present study was to report on the inhibitory effect of the novel compound C150 on the EMT of pancreatic cancer cells. C150 inhibited cell proliferation in multiple pancreatic cancer cells with IC50 values of 1-2.5 μM, while in an non-cancerous pancreatic epithelial cell line hTERT-HPNE the IC50 value was >12.5 μM. C150 significantly inhibited pancreatic cancer cell migration and invasion, as demonstrated by 3-dimensional cell invasion, wound healing and Boyden chamber Transwell migration-invasion assays. Moreover, C150 treatment decreased MMP-2 gene expression in PANC-1 cells and reduced MMP-2 activity in gelatin zymography assay. In an orthotopic mouse model of pancreatic cancer, C150 significantly reduced tumor growth at the dose of 15 mg/kg by intraperitoneal injection three times per week. Furthermore, C150 enhanced protein degradation of Snail, an important EMT-promoting transcription factor, and decreased the expression of the mesenchymal marker N-cadherin, while it increased the expression of the epithelial markers zonula occludens-1 and claudin-1. The findings of the present study suggested that C150 is a novel EMT inhibitor that may be promising for inhibiting pancreatic cancer growth and metastasis.

scholarly journals Astragaloside-IV Inhibits Pancreatic Cancer Cell Proliferation in Vitro and in Vivo by Inducing Cell Cycle Arrest and Apoptosis

2022 ◽  
Author(s):  
Guodong Chen ◽  
Chengming Ding ◽  
Weiping Tang ◽  
Shuo Qi ◽  
Pengyu Zhou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Pancreatic Cell ◽  
Pancreatic Cancer Cells

Abstract Astragaloside IV (AS-IV) or 3-O-β-D-xylopyranosyl-6-O-β-D-glucopyranosylcyl-cloastragenol is a bioactive saponin extract from the root of Astragalus membranaceus. It has been proven to have an anti-tumor effect in a variety of tumors by inducing cell apoptosis and inhibiting cell proliferation. Its effects on pancreatic cancer have not been investigated. This study investigated the effects of AS-IV on proliferation, apoptosis and migration of pancreatic cancer cells in vitro and in vivo and explored its underlying mechanism. Pancreatic cancer cell lines SW1990 and Panc-1were treated with different doses of AS-IV. Plate clonality, CCK-8, EDU and flow cytometry were used to explore the effect of AS-IV on pancreatic cancer cell proliferation and cell cycle in vitro. Wound healing was used to investigate the effects of AS-IV on pancreatic cell migration. The protein expression levels of Bax/Bcl2, caspase3/7, cyclin D1, cyclin E and CDK4 were analyzed by western blotting. The results showed that AS-IV significantly inhibited tumor cell proliferation and cell cycle, induced apoptosis both in vitro and vivo on a dose-dependent basis and significantly inhibited the growth of pancreatic cell xenograft tumor in nude mice. Wound healing assays indicated that AS-IV also inhibited the migration of pancreatic cancer cells in a dose-dependent manner. This research confirmed that AS-IV inhibited pancreatic cancer cell proliferation by blocking the cell cycle and inducing apoptosis. It was hypothesized from this experiment that the potential mechanism of AS-IV inducing apoptosis of pancreatic cancer cells may be understood by activating the Bcl2/Bax/Caspase-3/Caspase-7 signaling pathway.

scholarly journals The Effects of 2′,4′-Dihydroxy-6′-methoxy-3′,5′- dimethylchalcone from Cleistocalyx operculatus Buds on Human Pancreatic Cancer Cell Lines

Molecules ◽  
2019 ◽  
Vol 24 (14) ◽  
pp. 2538 ◽  
Author(s):  
Huynh Tuan ◽  
Bui Minh ◽  
Phuong Tran ◽  
Jeong Lee ◽  
Ha Oanh ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Caspase 3 ◽  
Pancreatic Cancer Cell ◽  
Human Pancreatic Cancer ◽  
Human Pancreatic Cancer Cell ◽  
Cleistocalyx Operculatus ◽  
Pancreatic Cancer Cells

2′,4′-Dihydroxy-6’-methoxy-3′,5′-dimethylchalcone (DMC), a principal natural chalcone of Cleistocalyx operculatus buds, suppresses the growth of many types of cancer cells. However, the effects of this compound on pancreatic cancer cells have not been evaluated. In our experiments, we explored the effects of this chalcone on two human pancreatic cancer cell lines. A cell proliferation assay revealed that DMC exhibited concentration-dependent cytotoxicity against PANC-1 and MIA PACA2 cells, with IC50 values of 10.5 ± 0.8 and 12.2 ± 0.9 µM, respectively. Treatment of DMC led to the apoptosis of PANC-1 by caspase-3 activation as revealed by annexin-V/propidium iodide double-staining. Western blotting indicated that DMC induced proteolytic activation of caspase-3 and -9, degradation of caspase-3 substrate proteins (including poly[ADP-ribose] polymerase [PARP]), augmented bak protein level, while attenuating the expression of bcl-2 in PANC-1 cells. Taken together, our results provide experimental evidence to support that DMC may serve as a useful chemotherapeutic agent for control of human pancreatic cancer cells.

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