scholarly journals Nobiletin Inhibits Cell Growth, Migration and Invasion, and Enhances the Anti-Cancer Effect of Gemcitabine on Pancreatic Cancer Cells

2021 ◽  
Vol 16 (4) ◽  
pp. 1934578X2110040
Author(s):  
Xiang Ren ◽  
Yuran Ma ◽  
Xiao Wang ◽  
Xuetao Xu ◽  
Panpan Wu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Pancreatic Cancer Cells ◽  
Underlying Mechanisms ◽  
Sphere Formation

Natural products are very promising adjuvants with a variety of biological activities. Nobiletin, a citrus polymethoxyflavone, has been shown to exert an anticancer effect in various cell lines. In this study, we investigated the effects of nobiletin on cell viability, sphere formation, migration and invasion of pancreatic cancer cells, and the underlying mechanisms. Our results demonstrate that nobiletin significantly inhibited PANC-1 cell migration and invasion, and these effects were associated with downregulation of MMP-2. We also found that nobiletin, in a low concentration, exhibited a strong inhibitory effect on sphere formation. The potential molecular mechanisms were related to significant downregulation of p-mTOR and p-STAT3. Furthermore, we found that nobiletin combined with gemcitabine synergistically inhibited PANC-1 cell viability and sphere formation. The underlying mechanisms of the synergistic inhibition on growth were associated with decreases in p-STAT3 expression. Overall, our results suggest that nobiletin may be a promising candidate for pancreatic cancer adjuvant treatment.

Mesoporous TiO2 Nanaoparticles Inhibits Malignant Pancreatic Cancer Cells Through STAT Pathway

2021 ◽  
Vol 13 (9) ◽  
pp. 1716-1723
Author(s):  
Jie Li ◽  
Chao Xu ◽  
Yueyue Lu ◽  
Yan Zhang ◽  
Xiaoping Tan
Keyword(s):  
Pancreatic Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Inhibitory Effect ◽  
Positive Control ◽  
Control Group ◽  
Blank Group ◽  
Pancreatic Cancer Cells ◽  
Experimental Group ◽  
Stat Pathway

Nanoparticles are known to have recognition ability for targeted delivery, and are thus widely used in the treatments of diseases. Mesoporous nano-titanium dioxide (TiO2) nanoparticles have characteristics of nanomaterials and their porous structure with high surface area strengthens their drug-loading capacity and targeting ability. This study aimed to investigate the effect of mesoporous nano-TiO2 on pancreatic cancer cells and STAT pathway activity. Initially, we prepared mesoporous TiO2 nanoparticles that were characterized. Pancreatic cancer cells were co-cultured with mesoporous nano-TiO2 nanoparticles at different concentrations (0.1 μg/mL, 0.5 μg/mL, 1 μg/mL, 5 μg/mL, and 10 μg/mL) or 10 μg/mL nano-TiO2 (positive control group) or cells cultured alone (blank group). Cell viability was determined at several specific time points (24 h, 48 h, and 72 h). Transwell assay and scratching assay were conducted to determine the number of migrated and invaded cells. STAT3 and JAK2 expressions were examined by RT-qPCR and Western blot analysis. The prepared mesoporous nano-TiO2 exhibited sharp diffraction peaks with enhanced intensity and diffraction rings. STAT pathway was activated in pancreas cancer cells, which had more fluorescent cells than normal cells. The presence of mesoporous nano-TiO2 nanoparticles suppressed cancer cell viability and their inhibition rate increased with increased of nano-TiO2 concentration. The concentration of 10 μg/mL exhibited greatest inhibitory effect and 10 μg/mL mesoporous nano-TiO2 thus was chosen for experimental group. The width of the scratch in the experimental group (19.97±0.82 mm) was higher than in the blank group and positive control group (P < 0.05); 10 μg/mL mesoporous nano-TiO2 significantly decreased the number of invaded cells (71.97±17.84) and number of cell clones (156.91±31.03) (P < 0.05). The expression levels of STAT3 (0.41±0.06 μg/μL) and JAK2 (0.39±0.04 ug/ul) were diminished by treatment with mesoporous nano-TiO2. Mesoporous nano-TiO2 inhibits pancreatic cancer cell growth and STAT expression, as its inhibitory effect depends on its concentration. These findings might provide a novel insight into nanoparticle-based treatment for pancreatic cancer.

scholarly journals α-Mangostin Suppresses the Viability and Epithelial-Mesenchymal Transition of Pancreatic Cancer Cells by Downregulating the PI3K/Akt Pathway

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Qinhong Xu ◽  
Jiguang Ma ◽  
Jianjun Lei ◽  
Wanxing Duan ◽  
Liang Sheng ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Complementary Alternative Medicine ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Matrigel Invasion ◽  
Pancreatic Cancer Cells

α-Mangostin, a natural product isolated from the pericarp of the mangosteen fruit, has been shown to inhibit the growth of tumor cells in various types of cancers. However, the underlying molecular mechanisms are largely unclear. Here, we report thatα-mangostin suppressed the viability and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells through inhibition of the PI3K/Akt pathway. Treatment of pancreatic cancer BxPc-3 and Panc-1 cells withα-mangostin resulted in loss of cell viability, accompanied by enhanced cell apoptosis, cell cycle arrest at G1 phase, and decrease of cyclin-D1. Moreover, Transwell and Matrigel invasion assays showed thatα-mangostin significantly reduced the migration and invasion of pancreatic cancer cells. Consistent with these results,α-mangostin decreased the expression of MMP-2, MMP-9, N-cadherin, and vimentin and increased the expression of E-cadherin. Furthermore, we found thatα-mangostin suppressed the activity of the PI3K/Akt pathway in pancreatic cancer cells as demonstrated by the reduction of the Akt phosphorylation byα-mangostin. Finally,α-mangostin significantly inhibited the growth of BxPc-3 tumor mouse xenografts. Our results suggest thatα-mangostin may be potentially used as a novel adjuvant therapy or complementary alternative medicine for the management of pancreatic cancers.

Oxidovanadium(IV) Complex Disrupts Mitochondrial Membrane Potential and Induces Apoptosis in Pancreatic Cancer Cells

2020 ◽  
Vol 21 (1) ◽  
pp. 71-83
Author(s):  
Szymon Kowalski ◽  
Aleksandra Tesmar ◽  
Artur Sikorski ◽  
Iwona Inkielewicz-Stępniak
Keyword(s):  
Pancreatic Cancer ◽  
Membrane Potential ◽  
Cytotoxic Activity ◽  
Cancer Cells ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Vanadium Complexes ◽  
Pancreatic Cancer Cells

Background: At the present time, there is a growing interest in metal-based anticancer agents. Metal complexes exhibit many valuable clinical properties, however, due to toxicity, only a few clinically useful complexes have been discovered. It has been demonstrated that synthetic vanadium complexes exhibit many biological activities, including anti-cancer properties, however, cellular and molecular mechanisms still are not fully understood. Objective: This investigation examined the potential effects of three newly synthesized oxidovanadium(IV) complexes with 2-amino-3-hydroxypyridine against pancreatic cancer cells. Methods: We measured cytotoxicity by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, antiproliferative activity by bromodeoxyuridine assay and necrosis as well as late apoptosis by lactate dehydrogenase assay. Reactive oxygen species generation, apoptosis and mitochondrial membrane potential were determined by a flow cytometry technique. Cell morphology was evaluated by using a transmission electron microscope. Results: The results showed that oxidovanadium(IV) complexes were cytotoxic on pancreatic cancer cells (PANC-1 and MIA PaCa2) over the concentration range of 12.5-200μM, following 48h incubation. Additionally, the cellular mechanism of cytotoxic activity of [2-NH2-3-OH(py)H]4[V2O2(pmida)2]·6H2O (V3) complex was dependent on ROS generation, induction apoptosis with simultaneous disruption of mitochondrial membrane potential. Conclusion: We have proven that oxidovanadium (IV) complexes show therapeutic potential in pancreatic cancer therapy. The results of our research will help to understand the cellular mechanisms of the cytotoxic activity of the vanadium complexes and will allow a more effective design structure of new vanadium-based compounds in the future.

Su1863 Tenascin C in Cancer Stroma Induces Migration and Invasion of Pancreatic Cancer Cells by Interaction With Fibronectin

2014 ◽  
Vol 146 (5) ◽  
pp. S-488
Author(s):  
Hideyuki Yoshitomi ◽  
Hiroaki Shimizu ◽  
Masayuki Ohtsuka ◽  
Atsushi Kato ◽  
Katsunori Furukawa ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Tenascin C ◽  
Cancer Stroma ◽  
Pancreatic Cancer Cells

scholarly journals Bitter melon juice targets molecular mechanisms underlying gemcitabine resistance in pancreatic cancer cells

2015 ◽  
Vol 46 (4) ◽  
pp. 1849-1857 ◽  
Author(s):  
RANGANATHA R. SOMASAGARA ◽  
GAGAN DEEP ◽  
SANGEETA SHROTRIYA ◽  
MANISHA PATEL ◽  
CHAPLA AGARWAL ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Bitter Melon ◽  
Gemcitabine Resistance ◽  
Pancreatic Cancer Cells

scholarly journals Long Non-coding RNA DLEU2L Targets miR-210-3p to Suppress Gemcitabine Resistance in Pancreatic Cancer Cells via BRCA2 Regulation

2021 ◽  
Vol 8 ◽  
Author(s):  
Fei Xu ◽  
Heshui Wu ◽  
Jiongxin Xiong ◽  
Tao Peng
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Aerobic Glycolysis ◽  
Critical Role ◽  
Migration And Invasion ◽  
Pancreatic Cell ◽  
Clinical Issue ◽  
Pancreatic Cancer Cells

Gemcitabine (GEM) resistance remains a challenging clinical issue to overcome in chemotherapy against pancreatic cancer. We previously demonstrated that miR-210 derived from pancreatic cancer stem cells enhanced the GEM-resistant properties of pancreatic cancer cells, thus identifying miR-210 as an oncogenic miRNA. Herein, we report the existence of an upstream effector that acts as a competing endogenous RNA (ceRNA) to miR-210. Bioinformatic screening was performed to identify lncRNAs with a binding relationship to miR-210. Overexpression and interference vectors were constructed to demonstrate the effect of ceRNA activity in pancreatic cell behavior, both in vitro and in vivo. DLEU2L (deleted in lymphocytic leukemia 2-like), which is expressed at low levels in pancreatic cancer tissues, was shown to exhibit a binding relationship with miR-210-3p. Overexpression of DLEU2L and silencing of miR-210-3p suppressed the proliferation, migration, and invasion of pancreatic cancer cells while promoting apoptosis. These effects occurred via the inhibition of the Warburg effect (aerobic glycolysis) and AKT/mTOR signaling. In addition, we showed that BRCA2 is a target gene of miR-210-3p, and the downregulation of miR-210-3p by DLEU2L effectively induced an upregulation of BRCA2 via the ceRNA mechanism. In vivo, DLEU2L overexpression and miR-210-3p interference suppressed pancreatic tumor progression, consistent with the results of in vitro studies. The findings of our study establish DLEU2L as a ceRNA to miR-210-3p and reveal the critical role of the DLEU2L/miR-210-3p crosstalk in targeting GEM resistance.

scholarly journals Identification of phosphoenolpyruvate carboxykinase 1 as a potential therapeutic target for pancreatic cancer

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Xiao-ren Zhu ◽  
Shi-qing Peng ◽  
Le Wang ◽  
Xiao-yu Chen ◽  
Chun-xia Feng ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Therapeutic Target ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Human Pancreatic Cancer ◽  
Migration And Invasion ◽  
Potential Therapeutic Target ◽  
Protein Levels ◽  
Pancreatic Cancer Cells

AbstractPancreatic cancer is the third leading cause of cancer-related mortalities and is characterized by rapid disease progression. Identification of novel therapeutic targets for this devastating disease is important. Phosphoenolpyruvate carboxykinase 1 (PCK1) is the rate-limiting enzyme of gluconeogenesis. The current study tested the expression and potential functions of PCK1 in pancreatic cancer. We show that PCK1 mRNA and protein levels are significantly elevated in human pancreatic cancer tissues and cells. In established and primary pancreatic cancer cells, PCK1 silencing (by shRNA) or CRISPR/Cas9-induced PCK1 knockout potently inhibited cell growth, proliferation, migration and invasion, and induced robust apoptosis activation. Conversely, ectopic overexpression of PCK1 in pancreatic cancer cells accelerated cell proliferation and migration. RNA-seq analyzing of differentially expressed genes (DEGs) in PCK1-silenced pancreatic cancer cells implied that DEGs were enriched in the PI3K-Akt-mTOR cascade. In pancreatic cancer cells, Akt-mTOR activation was largely inhibited by PCK1 shRNA, but was augmented after ectopic PCK1 overexpression. In vivo, the growth of PCK1 shRNA-bearing PANC-1 xenografts was largely inhibited in nude mice. Akt-mTOR activation was suppressed in PCK1 shRNA-expressing PANC-1 xenograft tissues. Collectively, PCK1 is a potential therapeutic target for 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.

scholarly journals LINC01121 Inhibits Cell Apoptosis While Facilitating Proliferation, Migration, and Invasion Though Negative Regulation of the Camp/PKA Signaling Pathway via GLP1R

2018 ◽  
Vol 47 (3) ◽  
pp. 1007-1024 ◽  
Author(s):  
Yi-Gang Qian ◽  
Zhou Ye ◽  
Hai-Yong Chen ◽  
Zhen Lv ◽  
Ai-Bin Zhang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Microarray Data ◽  
Cell Apoptosis ◽  
Migration And Invasion ◽  
Protein Levels ◽  
Pancreatic Cancer Cells ◽  
Significant Difference

Background/Aims: Pancreatic cancer is an aggressive malignancy as a result of highly metastatic potential. The current study was carried out to alter the expression of LINC01121 in pancreatic cancer, with the aim of elucidating its effects on the biological processes of cell proliferation, migration, invasion, and apoptosis. We hypothesized that both the GLP1R gene and cAMP/PKA signaling pathway participate in the aforementioned process. Methods: Microarray data (GSE14245, GSE27890 and GSE16515) and annotating probe files linked to pancreatic cancer were downloaded through the GEO database. The Multi Experiment Matrix (MEM) site was used to predict the target gene of lncRNA. Both pancreatic cancer tissues (n = 56) and paracancerous tissues (n = 45) were collected from patients diagnosed with pancreatic cancer. Immunohistochemistry was applied to identify the positive expression rate of GLP1R protein. Isolated pancreatic cancer cells and PANC-1 cells were independently classified into the blank, negative control (NC), LINC01121 vector, siRNA-LINC01121, siRNA-GLP1R and siRNA-LINC01121 + siRNA-GLP1R groups. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were applied to detect the expressions of LINC01121, GLP1R, cAMP, PKA, CREB, Bcl-2, Bad and PCNA. Cell proliferation, migration, invasion, cycle progression, and apoptosis were examined by MTT assay, scratch test, Transwell assay and flow cytometry analyses of Annexin V-FITC/PI staining. Results: Observations were made indicating that LINC01121 was highly expressed, while low expressions of GLP1R in pancreatic cancer were detected based on microarray data, which was largely in consistent with the data collected of LINC01121 and GLP1R within the tissues. The target prediction program and luciferase activity analysis was testament to the notion suggesting that GLP1R was indeed a target of LINC01121. In contrast to the blank and NC groups, the LINC01121 vector group exhibited increased expressions of LINC01121; decreased mRNA and protein levels of GLP1R, Bad, cAMP, and PKA; increased protein levels of CREB, Bcl-2, PCNA, p-PKA and p-CREB; increased cell proliferation, migration and invasion; and decreased cell apoptosis. There was no significant difference detected among the blank, NC, and siRNA-LINC01121 + siRNA-GLP1R groups, except that decreased LINC01121 expression was determined in the siRNA-LINC01121 + siRNA-GLP1R group. Parallel data were observed in the pancreatic cancer cells and PANC-1 cells. Conclusion: The current study presents evidence indicating that LINC01121 might inhibit apoptosis while acting to promote proliferation, migration, and invasion of pancreatic cancer cells, supplementing the stance held that LINC01121 functions as a tumor promoter by means of its involvement in the process of translational repression of the GLP1R and inhibition of the cAMP/PKA signaling pathway.

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