scholarly journals Mitofusin2 Induces Cell Autophagy of Pancreatic Cancer through Inhibiting the PI3K/Akt/mTOR Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ran Xue ◽  
Qinghua Meng ◽  
Di Lu ◽  
Xinjuan Liu ◽  
Yanbin Wang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Mtor Signaling ◽  
Biological Functions ◽  
Mtor Signaling Pathway ◽  
Pancreatic Cancer Cells

Aim. Pancreatic cancer is one of the most quickly fatal cancers around the world. Burgeoning researches have begun to prove that mitochondria play a crucial role in cancer treatment. Mitofusin2 (Mfn2) plays an indispensable role in mitochondrial fusion and adjusting function. However, the role and underlying mechanisms of Mfn2 on cell autophagy of pancreatic cancer is still unclear. Our aim was to explore the effect of Mfn2 on multiple biological functions involving cell autophagy in pancreatic cancer. Methods. Pancreatic cancer cell line, Aspc-1, was treated with Ad-Mfn2 overexpression. Western blotting, caspase-3 activity measurement, and CCK-8 and reactive oxygen species (ROS) assay were used to examine the effects of Mfn2 on pancreatic cancer autophagy, apoptosis, cell proliferation, oxidative stress, and PI3K/Akt/mTOR signaling. The expression of tissue Mfn2 was detected by immunohistochemical staining. Survival analysis of Mfn2 was evaluated by OncoLnc. Results. Mfn2 improved the expression of LC3-II and Bax and downregulated the expression of P62 and Bcl-2 in pancreatic cancer cells. Meanwhile, Mfn2 also significantly inhibited the expression of p-PI3K, p-Akt, and p-mTOR proteins in pancreatic cancer cells. In addition, Mfn2 inhibited pancreatic cancer cell proliferation and ROS production. Assessment of Kaplan-Meier curves showed that Mfn2− pancreatic cancer has a worse prognosis than Mfn2+ pancreatic cancer has. Conclusions. Our finding suggests that Mfn2 induces cell autophagy of pancreatic cancer through inhibiting the PI3K/Akt/mTOR signaling pathway. Meanwhile, Mfn2 also influences multiple biological functions of pancreatic cancer cells. Mfn2 may act as a therapeutic target in pancreatic cancer treatment.

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.

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 Silencing of the DJ-1 (PARK7) gene sensitizes pancreatic cancer to erlotinib inhibition

2019 ◽  
Author(s):  
Xiangyi He ◽  
Yunwei Sun ◽  
Rong Fan ◽  
jing Sun ◽  
Douwu Zou ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Kinase Inhibitor ◽  
Egfr Tyrosine Kinase Inhibitor ◽  
Pancreatic Cancer Cells

Abstract Abstract AIMS: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib, in combination with gemcitabine, has been shown to be a promising therapy in the treatment of pancreatic cancer. Our previous study showed that DJ-1 promotes invasion and metastasis of pancreatic cancer cells by activating SRC/ERK/uPA. The aim of this study was to evaluate whether silencing DJ-1 expression can sensitize pancreatic cancer cells to erlotinib treatment. METHODS: Knockdown of DJ-1 expression, combined with erlotinib treatment, was performed in the pancreatic cancer cell lines BxPC-3 and PANC-1. Cell proliferation was assessed with the CCK-8 assay and BrdU incorporation, while apoptosis was measured using terminal deoxynucleotidyl ransferase (TdT)-mediated dUTP nick-end labeling. RAS activity and activation of the downstream pathways involving AKT and ERK1/2 were explored to determine the underlying mechanism. RESULTS: Knockdown of DJ-1 expression accelerated erlotinib-induced cell apoptosis, and improved the inhibitory effect of erlotinib on pancreatic cancer cell proliferation in vitro and in xenograft tumor growth in vivo. Knockdown of DJ-1 decreased K-RAS expression, membrane translocation, and activity in BxPC-3 cells. Knockdown of DJ-1 also decreased K-RAS, H-RAS, and N-RAS expression in PANC-1 cells. Knockdown of DJ-1 synergistically inhibited AKT and ERK1/2 phosphorylation with erlotinib in pancreatic cancer cells. CONCLUSIONS: DJ-1 may activate the RAS pathway, reinforcing erlotinib drug resistance. Blocking DJ-1 in combination with the EGFR tyrosine kinase inhibitor erlotinib may be an attractive therapeutic target in pancreatic cancer.

scholarly journals Silencing of the DJ-1 (PARK7) gene sensitizes pancreatic cancer to erlotinib inhibition

2019 ◽  
Author(s):  
Xiangyi He ◽  
Yunwei Sun ◽  
Rong Fan ◽  
jing Sun ◽  
Douwu Zou ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Kinase Inhibitor ◽  
Egfr Tyrosine Kinase Inhibitor ◽  
Pancreatic Cancer Cells

Abstract Background: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib, in combination with gemcitabine, has been shown to be a promising therapy in the treatment of pancreatic cancer. Our previous study showed that DJ-1 promotes invasion and metastasis of pancreatic cancer cells by activating SRC/ERK/uPA. The aim of this study was to evaluate whether silencing DJ-1 expression can sensitize pancreatic cancer cells to erlotinib treatment. METHODS: Knockdown of DJ-1 expression, combined with erlotinib treatment, was performed in the pancreatic cancer cell lines BxPC-3, PANC-1 and MiaPACa-2. Cell proliferation was assessed with the CCK-8 assay and BrdU incorporation, while apoptosis was measured using terminal deoxynucleotidyl ransferase (TdT)-mediated dUTP nick-end labeling. RAS activity and activation of the downstream pathways involving AKT and ERK1/2 were explored to determine the underlying mechanism. RESULTS: Knockdown of DJ-1 expression accelerated erlotinib-induced cell apoptosis, and improved the inhibitory effect of erlotinib on pancreatic cancer cell proliferation in vitro and in xenograft tumor growth in vivo . Knockdown of DJ-1 decreased K-RAS expression, membrane translocation, and activity in BxPC-3 cells. Knockdown of DJ-1 also decreased K-RAS, H-RAS, and N-RAS expression in PANC-1 and MiaPACa-2 cells. Knockdown of DJ-1 synergistically inhibited AKT and ERK1/2 phosphorylation with erlotinib in pancreatic cancer cells. CONCLUSIONS: DJ-1 may activate the RAS pathway, reinforcing erlotinib drug resistance. Blocking DJ-1 in combination with the EGFR tyrosine kinase inhibitor erlotinib may be an attractive therapeutic target in pancreatic cancer.

Gemcitabine induces apoptosis and autophagy via the AMPK/mTOR signaling pathway in pancreatic cancer cells

2018 ◽  
Vol 65 (5) ◽  
pp. 665-671 ◽  
Author(s):  
Jinhui Zhu ◽  
Yan Chen ◽  
Yun Ji ◽  
Yuanquan Yu ◽  
Yun Jin ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Pancreatic Cancer Cells

scholarly journals CircRHOT1 Mediated Cell Proliferation, Apoptosis and Invasion of Pancreatic Cancer Cells by Sponging miR-125a-3p

2020 ◽  
Author(s):  
Sunkai Ling ◽  
Yanru He ◽  
Xiaoxue Li ◽  
Mingyue Hu ◽  
Yu Ma ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Biological Function ◽  
Diagnostic Marker ◽  
Biological Functions ◽  
Normal Tissues ◽  
Qrt Pcr ◽  
Pancreatic Cancer Cells ◽  
Cancer Tissues

Abstract Background: The present study aimed to investigate the mechanistic biological function of circRHOT1 in pancreatic cancer cells.Methods: The expression of circRHOT1 and miR-125a-3p in pancreatic cancer tissues and their paired adjacent normal tissues was quantified by qRT-PCR. By knocking down or overexpressing circRHOT1 and miR-125a-3p in pancreatic cancer cells, their functions and potential mechanisms were explored.Results: circRHOT1 was overexpressed in pancreatic cancer tissues and cell lines, and it was found to directly bind to miR-125a-3p, acting as an endogenous sponge to inhibit its activity. Knockdown of circRHOT1 expression significantly inhibited proliferation as well as invasion, and it promoted apoptosis of pancreatic cancer cells via the regulation of E2F3 through the targeting of miR-125a-3p.Conclusion: Taken together, our results demonstrated that circRHOT1 plays critical roles in regulating the biological functions of pancreatic cancer cells, suggesting that circRHOT1 may serve as a potential diagnostic marker and therapeutic target for patients with pancreatic cancer.

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.

Akt/mTOR signaling pathway is crucial for gemcitabine resistance induced by Annexin II in pancreatic cancer cells

2012 ◽  
Vol 178 (2) ◽  
pp. 758-767 ◽  
Author(s):  
Shingo Kagawa ◽  
Shigetsugu Takano ◽  
Hideyuki Yoshitomi ◽  
Fumio Kimura ◽  
Mamoru Satoh ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Annexin Ii ◽  
Mtor Signaling Pathway ◽  
Gemcitabine Resistance ◽  
Pancreatic Cancer Cells

scholarly journals Aspirin therapy reduces the ability of platelets to promote colon and pancreatic cancer cell proliferation: Implications for the oncoprotein c-MYC

2017 ◽  
Vol 312 (2) ◽  
pp. C176-C189 ◽  
Author(s):  
Annachiara Mitrugno ◽  
Joanna L. Sylman ◽  
Anh T. P. Ngo ◽  
Jiaqing Pang ◽  
Rosalie C. Sears ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Metastatic Cancer ◽  
Pancreatic Cancer Cell Line ◽  
Cancer Cell Line ◽  
Cancer Cell Proliferation

Aspirin, an anti-inflammatory and antithrombotic drug, has become the focus of intense research as a potential anticancer agent owing to its ability to reduce tumor proliferation in vitro and to prevent tumorigenesis in patients. Studies have found an anticancer effect of aspirin when used in low, antiplatelet doses. However, the mechanisms through which low-dose aspirin works are poorly understood. In this study, we aimed to determine the effect of aspirin on the cross talk between platelets and cancer cells. For our study, we used two colon cancer cell lines isolated from the same donor but characterized by different metastatic potential, SW480 (nonmetastatic) and SW620 (metastatic) cancer cells, and a pancreatic cancer cell line, PANC-1 (nonmetastatic). We found that SW480 and PANC-1 cancer cell proliferation was potentiated by human platelets in a manner dependent on the upregulation and activation of the oncoprotein c-MYC. The ability of platelets to upregulate c-MYC and cancer cell proliferation was reversed by an antiplatelet concentration of aspirin. In conclusion, we show for the first time that inhibition of platelets by aspirin can affect their ability to induce cancer cell proliferation through the modulation of the c-MYC oncoprotein.

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