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 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.

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.

Identifying Functional Differences Between Protein S and Gas-6 in Pancreatic Cancer

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2571-2571
Author(s):  
Cosette Zacarias ◽  
Vijaya Satish Sekhar Pilli ◽  
William E. Plautz ◽  
A'drianne Wells ◽  
Rinku Majumder
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Biology ◽  
Pancreatic Cancer Cell ◽  
Protein S ◽  
Cancer Cell Lines ◽  
Cancer Cell Proliferation

Abstract Introduction: Procoagulants such as Factor IX and thrombin play major roles in cancer cell proliferation and migration; however, a role for anticoagulant proteins in cancer biology has not been elucidated. The anticoagulant Protein S (PS), its homologous protein Growth Arrest Specific protein-6 (GAS-6), and the receptors for these proteins, Tyro-3, Axl and Mertk (TAM), are over expressed in many cancer cells. TAM family receptors regulate functions such as cell survival, proliferation, migration, and apoptosis. The consequences of activation of each of these receptors varies, although the mechanism that leads to different outcomes is unknown. We hypothesized that the PS and GAS-6 ligands are responsible for the variations in the functions of these signaling cascades. Methods: We used qPCR to analyze the pancreatic cancer cell lines Miapaca-2 and Panc-1 for variations in the expression of GAS-6 and PS. We sequestered PS and GAS-6 with antibodies and used FACS analysis to detect effects on the cell cycle and on cell cycle regulators. Results: GAS-6 was observed to be highly expressed in proliferating Miapaca-2 cells compared with Panc-1 cells, whereas there was no significant difference in PS mRNA levels between these cell lines. For the cell line Miapaca-2, antibody sequestration of GAS-6 arrested the cell cycle in S-phase and increased p53 phosphorylation; conversely, inhibition of PS reduced p53 phosphorylation. Conclusion: Our results indicate that PS and GAS-6 act antagonistically in controlling pancreatic cancer cell proliferation, and we hypothesize that the ratio of GAS-6 to PS expression is key to this regulation. We will further confirm our hypothesis by overexpressing and knocking down PS and GAS-6 in the pancreatic cancer cell lines. Disclosures No relevant conflicts of interest to declare.

scholarly journals EI24 Suppresses Tumorigenesis in Pancreatic Cancer via Regulating c-Myc

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Yi Zang ◽  
Lei Zhu ◽  
Tong Li ◽  
Qi Wang ◽  
Juanjuan Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Transmembrane Protein ◽  
Beclin 1 ◽  
Ductal Adenocarcinoma ◽  
Antitumor Effects ◽  
Pancreatic Cancer Cells

The EI24 autophagy-associated transmembrane protein is frequently associated with tumor growth and patient survival. In the present study, we found that EI24 was downregulated in pancreatic ductal adenocarcinoma (PDAC) tissues compared with adjacent normal tissues and was associated with cancer cell differentiation. Overexpression of EI24 suppressed cancer cell growth in vitro and in vivo and induced cell cycle S phase arrest, with no impact on caspase-dependent apoptosis. EI24 overexpression also resulted in reduced c-Myc expression, an oncogene in PDAC, accompanied with increased LC3B-II formation, increased Beclin-1, and diminished p62. Together, we propose that EI24 suppresses cell proliferation and prompts cell cycle arrest in pancreatic cancer cells by activating the autophagic lysosomal degradation of c-Myc. Our results suggest a potential mechanism underlying the antitumor effects of EI24 in PDAC and provide insight into the crosstalk between autophagy and cell proliferation involving a possible EI24/Beclin-1/p62/c-Myc signaling pathway.

scholarly journals Interactions with stromal cells promote a more oxidized cancer cell redox state in pancreatic tumors

2020 ◽  
Author(s):  
Rupsa Datta ◽  
Allison N. Lau ◽  
Sharanya Sivanand ◽  
Logan Florek ◽  
Jeffrey Wyckoff ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Redox State ◽  
Pancreatic Stellate Cells ◽  
Pancreatic Tumors ◽  
Cancer Cell Proliferation ◽  
Pancreatic Cancer Cells ◽  
Endogenous Fluorescence

AbstractAccess to electron acceptors supports oxidized biomass synthesis and can be limiting for cancer cell proliferation, but how cancer cells overcome this limitation in tumors is incompletely understood. Non-transformed cells in tumors can help cancer cells overcome metabolic limitations, particularly in pancreatic cancer, where pancreatic stellate cells (PSCs) promote cancer cell proliferation and tumor growth. However, whether PSCs affect the redox state of cancer cells is not known. By taking advantage of the endogenous fluorescence properties of reduced nicotinamide adenine dinucleotide cofactors and oxidized flavin adenine dinucleotide, we use optical imaging to assess the redox state of pancreatic cancer cells and PSCs and find that the redox state of cancer cells is more reduced while the redox state of PSCs is more oxidized. Direct interactions between PSCs and cancer cells promote a more oxidized state in cancer cells, suggesting that metabolic interactions between cancer cells and PSCs is a mechanism to overcome the redox limitations of cell proliferation in pancreatic cancer.

Downregulation of lncRNA AFAP1-AS1 by oridonin inhibits the epithelial-to-mesenchymal transition and proliferation of pancreatic cancer cells

2019 ◽  
Vol 51 (8) ◽  
pp. 814-825 ◽  
Author(s):  
Songmei Lou ◽  
Jian Xu ◽  
Bili Wang ◽  
Shuquan Li ◽  
Jun Ren ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cell Cycle Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Pancreatic Cancer Cell ◽  
Cycle Progression ◽  
Mesenchymal Transition ◽  
Pancreatic Cancer Cells

AbstractRecent studies have demonstrated that the expression of the long non-coding RNA (lncRNA) AFAP1-AS1 in pancreatic cancer is negatively correlated with survival and prognosis. However, the effects of oridonin and lncRNA AFAP1-AS1 on the epithelial-to-mesenchymal transition (EMT) and migration of pancreatic cancer cells have not been fully elucidated. Surgery is the only potentially curative method for pancreatic cancer, but postoperative recurrence and metastasis are common. The aim of the present study was to assess the effect of oridonin and lncRNA AFAP1-AS1 silencing on pancreatic cancer cells. The pancreatic cancer cell lines BxPC-3 and PANC-1 cells were transfected with siAFAP1-AS1 and its negative control (siNC). After that, oridonin was used to treat the siAFAP1-AS1-transfected cells. The expression of lncRNA AFAP1-AS1 was downregulated in the pancreatic cancer cell lines BxPC-3 and PANC-1. The apoptosis and cell cycle progression of pancreatic cancer cells were evaluated by flow cytometry and Hoechst 33258 staining. Metastasis and invasion of BxPC-3 and PANC-1 cells were detected by transwell migration assay, real-time cell analysis, and western blot analysis. Cells were transfected with the lentiviral siAFAP1-AS1 and siNC, and tumorigenesis was evaluated in BALB/C nude mice. Immunohistochemical examination was used to verify the effects of oridonin and siAFAP1-AS1 on pancreatic cancer. The results demonstrated that the combination of oridonin and siAFAP1-AS1 inhibited pancreatic cancer cell proliferation, induced apoptosis, arrested cell cycle progression, prevented the migration, regulated EMT-related protein expression in BxPC-3 and PANC-1 cells, and inhibited pancreatic cancer cell tumorigenicity and EMT in nude mice.

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.

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