Biodegradable nanoparticle-mediated K-ras down regulation for pancreatic cancer gene therapy

2015 ◽  
Vol 3 (10) ◽  
pp. 2163-2172 ◽  
Author(s):  
Chengbin Yang ◽  
Rui Hu ◽  
Tommy Anderson ◽  
Yucheng Wang ◽  
Guimiao Lin ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Gene Therapy ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Sirna Delivery ◽  
Cancer Gene Therapy ◽  
Migration And Invasion ◽  
Cancer Gene ◽  
Pancreatic Cancer Cells ◽  
Biodegradable Nanoparticle

Biodegradable nanoparticle-mediated K-ras siRNA delivery has shown inhibition of cell proliferation, migration and invasion in pancreatic cancer cells.

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.

Curcumin Inhibits Pancreatic Cancer Progression via Down-Regulation of miR-21-5p

2020 ◽  
Vol 18 (3) ◽  
pp. 236-240
Author(s):  
Li Junjian ◽  
Xu Qigang ◽  
Tao Chonglin
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
B Cell ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Promote Cell Proliferation ◽  
Pancreatic Cancer Cells

In this study, we investigated the role of curcumin in pancreatic cancer through the regulation of miR-21-5p. We first evaluated the expression of miR-21-5p in pancreatic cancer cells (ASPC-1) treated with different concentrations of curcumin. The results showed that curcumin effectively inhibited the expression of miR-21-5p in ASPC-1 cells in a dose-dependent manner. B cell translocation gene 2 was identified as a target gene of miR-21-5p. MiR-21-5p mimics could promote cell proliferation, migration, and invasion of ASPC-1, as well as decrease the expression of B cell translocation gene 2. Curcumin treatment inhibited cell proliferation, migration and invasion of ASPC-1, as well as increased the expression of B cell translocation gene 2. MiR-21-5p could reverse the inhibitory activities of curcumin on ASPC-1 cell proliferation, migration, and invasion. In conclusion, curcumin is capable of inhibiting the proliferation, migration and invasion of pancreatic cancer cells via down-regulating miR-21-5p-mediated B cell translocation gene 2.

scholarly journals Effects of ER-resident and secreted AGR2 on cell proliferation, migration, invasion, and survival in PANC-1 pancreatic cancer cells

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xian Hong ◽  
Zhi-Xuan Li ◽  
Jie Hou ◽  
Hui-Yu Zhang ◽  
Chun-Yan Zhang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Migration And Invasion ◽  
Pancreatic Cancer Cells ◽  
Egfr Expression ◽  
Extracellular Compartment ◽  
Survival Capacity ◽  
Overexpression System

Abstract Background Anterior gradient-2 (AGR2) is a proto-oncogene involved in tumorigenesis and cancer progression. AGR2, predominantly localized in the endoplasmic reticulum (ER), is also a secreted protein detected in the extracellular compartment in multiple cancers. However, the biological functions of intracellular and extracellular AGR2 remain to be elucidated. Methods Based on the biochemical structure of AGR2 protein, PANC-1 pancreatic cancer cells stably expressing ER-resident or secreted AGR2 were generated by a lentivirus-mediated stable overexpression system. The capacities of cell proliferation, migration, invasion and survival were assessed in PANC-1 stable cells. Moreover, EGFR expression and activation were determined to explore the possible mechanism of AGR2 roles in pancreatic cancer tumorigenesis. Results It was discovered that secreted AGR2, but not ER-resident AGR2, promotes cell proliferation, migration and invasion of PANC-1 cells. Moreover, the data indicated that both the ER-resident and the secreted AGR2 enhance the survival capacity of PANC-1 cells after tunicamycin-induced ER stress and gemcitabine treatment. However, EGFR expression and activation were not found to be involved in AGR2-dependent oncogenic phenotypes in PANC-1 cells. Conclusions Secreted AGR2 is predominantly involved in cell proliferation, migration and invasion in PANC-1 pancreatic cancer cells. Both secreted and ER-resident AGR2 contribute to the survival of PANC-1 cells under the challenging conditions. These findings provide insight into how different localizations of AGR2 have contributed to pancreatic cancer growth, metastasis, and drug sensitivity.

scholarly journals MiR-203 inhibits the proliferation, invasion, and migration of pancreatic cancer cells by down-regulating fibroblast growth factor 2

2020 ◽  
Author(s):  
Xi-Feng Fu ◽  
Hai-Chao Zhao ◽  
Chang-Zhou Chen ◽  
Kang Wang ◽  
Fei Gao ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Invasion And Metastasis ◽  
Invasion And Migration ◽  
Qrt Pcr ◽  
Pancreatic Cancer Cells ◽  
Fgf2 Expression ◽  
And Migration

AbstractBackgroundAberrant fibroblast growth factor 2 (FGF2) expression is a major cause of poor prognosis in pancreatic cancer. MiR-203 is a newly discovered microRNA (miRNA) that can affect the biological behavior of tumors. This study investigated whether miR-203 can regulate FGF2 expression and its role in pancreatic cancer cell proliferation, apoptosis, invasion, and migration.MethodsMiR-203 expression in different cell lines was examined by qRT-PCR, followed by the establishment of knockdown and overexpression cell models. We used the CCK-8 assay to examine cell proliferation and the annexin V-APC/7-AAD double-staining method to detect apoptosis. In addition, we used wound healing and transwell assays to investigate the effects of miR-203 on the migration and invasion of pancreatic cancer cells. The effects of miR-203 knockdown and overexpression on FGF2 mRNA expression were detected by qRT-PCR. We also overexpressed FGF2 and examined the effects of FGF2 overexpression on the proliferation, apoptosis, invasion, and migration of pancreatic cancer cells. The binding of miR-203 to FGF2 was assessed by a luciferase reporter assay.ResultsWe found that the miR-203 expression level was significantly down-regulated in pancreatic cancer cells compared to normal pancreatic cells. Functionally, the knockdown of miR-203 inhibited cell proliferation and increased apoptosis. Equally important, miR-203 reduced the migration and invasion of pancreatic cancer cells. In addition, we found that miR-203 overexpression inhibited FGF2 expression in pancreatic cancer cells by qRT-PCR. FGF2 overexpression significantly affected the proliferation, invasion, and metastasis of pancreatic cancer cells. Mechanistically, miR-203 base-paired with the FGF2 mRNA, resulting in the knockdown of the FGF2 mRNA and the down-regulation of the FGF2 protein.ConclusionsMiR-203 inhibits FGF2 expression, regulates the proliferation of pancreatic cancer cells, and inhibits the invasion and metastasis of pancreatic cancer cells.

Panax Notoginseng Saponins Promote Cell Death and Chemosensitivity in Pancreatic Cancer through the Apoptosis and Autophagy Pathways

2020 ◽  
Vol 20 ◽  
Author(s):  
Li-Chao Yao ◽  
Lun Wu ◽  
Wei Wang ◽  
Lu-Lu Zhai ◽  
Lin Ye ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Panax Notoginseng ◽  
Panax Notoginseng Saponins ◽  
Transwell Assay ◽  
Pancreatic Cancer Cells ◽  
New Strategy ◽  
Induced Apoptosis ◽  
Promote Cell Death

Background:: Panax Notoginseng Saponins (PNS) is used as traditional Chinese medicine for ischemic stroke and cardiovascular disease, it has been proven to possess anticancer activity recently. Objective:: In this study, we aimed to explore the anticancer curative effect and potential mechanisms of PNS in pancreatic cancer cells. Methods:: Pancreatic cancer Miapaca2 and PANC-1 cells were treated with PNS and Gemcitabine (Gem), respectively. Then the cell viability was assessed by CCK-8 assay, cell proliferation was tested by colony formation assay and EdU cell proliferation assay, cell migration and invasiveness were tested by wound healing assay and transwell assay respectively, and cell apoptosis was detected by flow cytometry. Finally, we detected the expression levels of proteins related to migration, apoptosis and autophagy through Western blotting. Results:: PNS not only inhibited the proliferation, migration, invasion and autophagy of Miapaca2 and PANC-1 cells, but also induced apoptosis and promoted chemosensitivity of pancreatic cancer cells to Gem. Conclusion:: PNS may exhibit cytotoxicity and increase chemosensitivity of pancreatic cancer cells to Gem by inhibiting autophagy and inducing apoptosis, providing a new strategy and potential treatment option for pancreatic cancer.

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 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.

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