Mesoporous TiO2 Nanaoparticles Inhibits Malignant Pancreatic Cancer Cells Through 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.

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

Natural Product Communications ◽

10.1177/1934578x211004062 ◽

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.

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The Radio-Sensitizing Effect of Pharmacological Concentration of Ascorbic Acid on Human Pancreatic Cancer Cells

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200612144124 ◽

2020 ◽

Vol 20 (16) ◽

pp. 1927-1932

Author(s):

Dian Dayer ◽

Mohammad R. Tabandeh ◽

Majid Kazemi

Keyword(s):

Pancreatic Cancer ◽

Ascorbic Acid ◽

Cell Viability ◽

Cancer Cells ◽

Cell Line ◽

Dna Fragmentation ◽

Human Pancreatic Cancer ◽

Control Group ◽

Ros Production ◽

Pancreatic Cancer Cells

Background: Previous studies reported the inevitable destructive effects of radiotherapy on normal adjacent cells. Ascorbic Acid (AA) has been proposed as an effective anti-cancer agent with no obvious effects on normal cells. Objective: The effects of Ascorbic acid in combination with radiotherapy on human pancreatic carcinoma cell line were studied. Methods: The human pancreatic cancer cells were cultured and divided into four groups: control group (A) without any treatment, group B that received 2Gy radiotherapy alone, group C that was treated with 4mM AA alone, and group D that was co-treated with AA and radiotherapy. Cell viability, DNA fragmentation, expression of apoptotic genes, and Reactive Oxygen Species (ROS) production were determined in treated cells. Results: There was a noticeable decrease in cell viability after treatment with AA (and/or) radiotherapy. All treated groups showed elevated ROS production, Bax/Bcl2 expression, DNA fragmentation, and cytotoxycity compared with the control group. Cells under combination therapy showed the most cytotoxicity. Conclusion: The results suggest that AA at a dose of 4mmol/l may be used as an effective radio-sensitizing agent in pancreatic cancer cell line.

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Low glucose enhanced metformin’s inhibitory effect on pancreatic cancer cells by suppressing glycolysis and inducing energy stress via up-regulation of miR-210-5p

Cell Cycle ◽

10.1080/15384101.2020.1796036 ◽

2020 ◽

Vol 19 (17) ◽

pp. 2168-2181

Author(s):

Minglei Ma ◽

Chifa Ma ◽

Pingping Li ◽

Chunxiao Ma ◽

Fan Ping ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Cells ◽

Inhibitory Effect ◽

Pancreatic Cancer Cells ◽

Energy Stress ◽

Low Glucose

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Fraction B From Catfish Epidermal Secretions Kills Pancreatic Cancer Cells, Inhibits CD44 Expression and Stemness, and Alters Cancer Cell Metabolism

Frontiers in Pharmacology ◽

10.3389/fphar.2021.659590 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jassim M. Al-Hassan ◽

Daoyan Wei ◽

Sharmistha Chakraborty ◽

Tara Conway ◽

Patrea Rhea ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Cells ◽

Glutamine Metabolism ◽

Stem Cell Marker ◽

Control Group ◽

Potential Candidate ◽

Cd44 Expression ◽

Tumor Bearing ◽

Pancreatic Cancer Cells

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer related death in western countries. The successful treatment of PDAC remains limited. We investigated the effect of Fraction B, which is a fraction purified from catfish (Arius bilineatus, Val.) skin secretions containing proteins and lipids, on PDAC biology both in-vivo and in-vitro. We report here that Fraction B potently suppressed the proliferation of both human and mouse pancreatic cancer cells in vitro and significantly reduced the growth of their relevant xenograft (Panc02) and orthotopic tumors (human Panc-1 cells) (p < 0.05). The Reverse Phase Protein Array (RPPA) data obtained from the tumor tissues derived from orthotopic tumor bearing mice treated with Fraction B showed that Fraction B altered the cancer stem cells related pathways and regulated glucose and glutamine metabolism. The down-regulation of the cancer stem cell marker CD44 expression was further confirmed in Panc-1 cells. CBC and blood chemistry analyses showed no systemic toxicity in Fraction B treated Panc-1 tumor bearing mice compared to that of control group. Our data support that Fraction B is a potential candidate for PDAC treatment.

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

Current Cancer Drug Targets ◽

10.2174/1568009618666180430123939 ◽

2019 ◽

Vol 19 (5) ◽

pp. 417-427 ◽

Cited By ~ 4

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.

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