scholarly journals Cardamonin Promotes the Apoptosis and Chemotherapy Sensitivity to Gemcitabine of Pancreatic Cancer Through Modulating the FOXO3a-FOXM1 Axis

Dose-Response ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 155932582110421
Author(s):  
Huapeng Sun ◽  
Na Zhang ◽  
Yiqiang Jin ◽  
Haisheng Xu
Keyword(s):  
Pancreatic Cancer ◽  
Biological Activities ◽  
Cell Counting ◽  
Loss Of Function ◽  
Chemotherapy Sensitivity ◽  
In Vivo Experiments ◽  
Pathway Expression ◽  
Foxm1 Expression

Cardamonin (CAR), a flavone existing in the Alpinia plant, has been found to modulate multiple biological activities, including antioxidant, anti-inflammatory, and anti-tumor effects. Nevertheless, the influence of CAR on pancreatic cancer (PC) is less understood. Here, we conducted in vitro and in vivo experiments to explore the functions of CAR on PC cells’ proliferation, apoptosis and chemosensitivity to gemcitabine (GEM). The growth of PC cells (including PANC-1 and SW1990) was evaluated by the cell counting kit-8 assay, colony formation assay and xenograft tumor experiment. Besides, the apoptosis was determined by flow cytometry and western blot (WB). Moreover, the FOXO3a-FOXM1 pathway expression was tested by reverse transcription-polymerase chain reaction and WB. Our data suggested that CAR restrained cell proliferation, growth and expedited apoptosis both in vitro and in vivo. Moreover, CAR sensitized PC cells to GEM. Mechanistically, CAR heightened FOXO3a while repressed FOXM1. Further loss-of-function assays revealed that down-regulating FOXO3a markedly dampened the anti-tumor effect induced by CAR and accelerated the FOXM1 expression. Our data confirmed that CAR exerted an anti-tumor function in PC dependently by modulating the FOXO3a-FOXM1 axis.

scholarly journals Oncogene APOL1 promotes proliferation and inhibits apoptosis via activating NOTCH1 signaling pathway in pancreatic cancer

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Jiewei Lin ◽  
Zhiwei Xu ◽  
Junjie Xie ◽  
Xiaxing Deng ◽  
Lingxi Jiang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathway ◽  
Density Lipoprotein ◽  
Human Pancreatic Cancer ◽  
Luciferase Reporter ◽  
Notch1 Signaling ◽  
In Vivo Experiments ◽  
Notch1 Signaling Pathway

AbstractAPOL1 encodes a secreted high-density lipoprotein, which has been considered as an aberrantly expressed gene in multiple cancers. Nevertheless, the role of APOL1 in the regulatory mechanisms of pancreatic cancer remains unknown and should be explored. We identified APOL1 was abnormally elevated in human pancreatic cancer tissues compared with that in adjacent tissues and was associated with poor prognosis. The effects of APOL1 in PC cell proliferation, cell cycle, and apoptosis was verified via functional in vitro and in vivo experiments. The results showed that knockdown of APOL1 significantly inhibited the proliferation and promoted apoptosis of pancreatic cancer. In addition, we identified APOL1 could be a regulator of NOTCH1 signaling pathway using bioinformatics tools, qRT-PCR, dual-luciferase reporter assay, and western blotting. In summary, APOL1 could function as an oncogene to promote proliferation and inhibit apoptosis through activating NOTCH1 signaling pathway expression in pancreatic cancer; therefore, it may act as a novel therapeutic target for pancreatic cancer.

scholarly journals Long noncoding RNA LINC00941 promotes pancreatic cancer progression by competitively binding miR-335-5p to regulate ROCK1-mediated LIMK1/Cofilin-1 signaling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jie Wang ◽  
Zhiwei He ◽  
Jian Xu ◽  
Peng Chen ◽  
Jianxin Jiang
Keyword(s):  
Pancreatic Cancer ◽  
Cell Growth ◽  
Cell Lines ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Loss Of Function ◽  
Mesenchymal Transition

AbstractAn accumulation of evidence indicates that long noncoding RNAs are involved in the tumorigenesis and progression of pancreatic cancer (PC). In this study, we investigated the functions and molecular mechanism of action of LINC00941 in PC. Quantitative PCR was used to examine the expression of LINC00941 and miR-335-5p in PC tissues and cell lines, and to investigate the correlation between LINC00941 expression and clinicopathological features. Plasmid vectors or lentiviruses were used to manipulate the expression of LINC00941, miR-335-5p, and ROCK1 in PC cell lines. Gain or loss-of-function assays and mechanistic assays were employed to verify the roles of LINC00941, miR-335-5p, and ROCK1 in PC cell growth and metastasis, both in vivo and in vitro. LINC00941 and ROCK1 were found to be highly expressed in PC, while miR-335-5p exhibited low expression. High LINC00941 expression was strongly associated with larger tumor size, lymph node metastasis, and poor prognosis. Functional experiments revealed that LINC00941 silencing significantly suppressed PC cell growth, metastasis and epithelial–mesenchymal transition. LINC00941 functioned as a molecular sponge for miR-335-5p, and a competitive endogenous RNA (ceRNA) for ROCK1, promoting ROCK1 upregulation, and LIMK1/Cofilin-1 pathway activation. Our observations lead us to conclude that LINC00941 functions as an oncogene in PC progression, behaving as a ceRNA for miR-335-5p binding. LINC00941 may therefore have potential utility as a diagnostic and treatment target in this disease.

scholarly journals CD44v10: An Antimetastatic Membrane Glycoprotein for Pancreatic Cancer

2003 ◽  
Vol 18 (2) ◽  
pp. 130-138 ◽  
Author(s):  
F. Navaglia ◽  
P. Fogar ◽  
E. Greco ◽  
D. Basso ◽  
A.L. Stefani ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Membrane Glycoprotein ◽  
Rt Pcr ◽  
In Vivo Experiments ◽  
Microtiter Plates ◽  
Pancreatic Metastases ◽  
Metastatic Behavior ◽  
Mrna Analysis

Aims The aims of this study were 1) to investigate the mRNA pattern of CD44 variants in three primary (MIA PaCa 2, PANC-1, PSN-1) and two metastatic (CAPAN-1, SUIT-2) pancreatic cancer (PC) cell lines; 2) to ascertain whether the genetic transfer of CD44s and CD44v10 modifies the adhesion of PC cells to the extracellular matrix (ECM) in vitro and their metastatic behavior in vivo. Methods CD44 mRNA analysis was done by means of RT-PCR. Adhesion to ECM the was assessed using coated microtiter plates. For the study of CD44v10 insertion in the CAPAN-1 line, liposome-mediated DNA transfer was used. SCID mice were employed for in vivo experiments. Results CD44v10 mRNA was not expressed by the CAPAN-1 nor by four of the six SUIT-2-derived clones. The stable expression of CD44v10 by modified CAPAN-1 significantly enhanced fibronectin adhesion. Mice without either liver or pancreatic metastases were more frequently found among the animals injected with modified (CD44v10 expressing) than with non-modified CAPAN-1. Conclusions 1) It is possible to differentiate between metastatic and non-metastatic PC cells on the basis of CD44v10 expression; 2) CD44v10 seems to be involved in mediating fibronectin adhesion in vitro and in counteracting metastases in vivo.

scholarly journals Long non-coding RNA NORAD promotes pancreatic cancer stem cell proliferation and self-renewal by blocking microRNA-202-5p-mediated ANP32E inhibition

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yu-Shui Ma ◽  
Xiao-Li Yang ◽  
Yu-Shan Liu ◽  
Hua Ding ◽  
Jian-Jun Wu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Viability ◽  
Luciferase Reporter ◽  
Cell Cycle Distribution ◽  
Loss Of Function ◽  
Self Renewal

Abstract Background Cancer stem cells (CSCs) are key regulators in the processes of tumor initiation, progression, and recurrence. The mechanism that maintains their stemness remains enigmatic, although the role of several long noncoding RNAs (lncRNAs) has been highlighted in the pancreatic cancer stem cells (PCSCs). In this study, we first established that PCSCs overexpressing lncRNA NORAD, and then investigated the effects of NORAD on the maintenance of PCSC stemness. Methods Expression of lncRNA NORAD, miR-202-5p and ANP32E in PC tissues and cell lines was quantified after RNA isolation. Dual-luciferase reporter assay, RNA pull-down and RIP assays were performed to verify the interactions among NORAD, miR-202-5p and ANP32E. We then carried out gain- and loss-of function of miR-202-5p, ANP32E and NORAD in PANC-1 cell line, followed by measurement of the aldehyde dehydrogenase activity, cell viability, apoptosis, cell cycle distribution, colony formation, self-renewal ability and tumorigenicity of PC cells. Results LncRNA NORAD and ANP32E were upregulated in PC tissues and cells, whereas the miR-202-5p level was down-regulated. LncRNA NORAD competitively bound to miR-202-5p, and promoted the expression of the miR-202-5p target gene ANP32E thereby promoting PC cell viability, proliferation, and self-renewal ability in vitro, as well as facilitating tumorigenesis of PCSCs in vivo. Conclusion Overall, lncRNA NORAD upregulates ANP32E expression by competitively binding to miR-202-5, which accelerates the proliferation and self-renewal of PCSCs.

scholarly journals Hypoxia-Related Gene FUT11 Promoted Pancreatic Cancer Progression Via Maintaining The Stabilization of PDK1

2021 ◽  
Author(s):  
Wenpeng Cao ◽  
Zhirui Zeng ◽  
Runsang Pan ◽  
Zhiwei He ◽  
Hao Wu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Growth ◽  
Western Blot ◽  
Cancer Progression ◽  
Pyruvate Dehydrogenase Kinase ◽  
Cell Counting ◽  
Luciferase Assay ◽  
Migration And Invasion

Abstract Background: Hypoxia participated in the occurrence and development of pancreatic cancer (PC). However, genes associated with hypoxia respond and their regulated mechanism in PC cells were unclear. The current research was aimed to illuminate the role and hypoxia regulated mechanism of fucosyltransferase 11 (FUT11) in the progression of PC.Methods: After predicting FUT11 as a key hypoxia associated gene in PC using bioinformatics analysis. The expression of FUT11 in PC using quantitative real-time fluorescent PCR, western blot and immunohistochemistry. The effects of FUT11 on PC cells proliferation, migration and invasion under normoxia and hypoxia were detected using Cell Counting Kit 8, 5-ethynyl-2’-deoxyuridine assay, colony formation assay and transwell assay. Spleen capsule injected liver metastasis and subcutaneously injected model were performed to confirm the effects of FUT11 in vivo. Furthermore, western blot, luciferase assay and immunoprecipitation were performed to explore the regulated relationship among FUT11, hypoxia-inducible factor 1α (HIF1α) and pyruvate dehydrogenase kinase 1 (PDK1) in PC.Results: FUT11 was markedly increased of PC cells in hypoxia, up-regulated in the PC clinical tissues, and predicted a poor outcome. Inhibition of FUT11 reduced PC cell growth and mobility of PC cells under normoxia and hypoxia conditions in vitro, and growth and mobility in vivo. FUT11 bind with PDK1 and regulated the expression PDK1 under normoxia and hypoxia. FUT11 knockdown significantly increased the degradation rate of PDK1 under hypoxia, while treatment with MG132 can relieve the degradation of PDK1 induced by FUT11 knockdown. Overexpression of PDK1 in PC cells under hypoxia conditions reversed the suppressiv impacts of FUT11 knockdown on PC cell growth and mobility. In addition, HIF1α bound to the enhancer of FUT11 and increased its expression, as well as co-expressing with FUT11 in PC tissues. Furthermore, overexpress of FUT11 partially rescued the suppressiv effects of HIF1α knockdown on PC cell growth and mobility in hypoxia conditions.Conclusion: Our data further implicate that hypoxia-induced FUT11 in PC contributes to proliferation and metastasis by maintaining the stability of PDK1, and suggest FUT11 maybe a novel and effective target for treatment of pancreatic cancer.

scholarly journals Scrophulariae Radix: An Overview of Its Biological Activities and Nutraceutical and Pharmaceutical Applications

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5250
Author(s):  
Hae-Jin Lee ◽  
Hae-Lim Kim ◽  
Dong-Ryung Lee ◽  
Bong-Keun Choi ◽  
Seung-Hwan Yang
Keyword(s):  
Biological Activities ◽  
Neuroprotective Effect ◽  
In Vivo Studies ◽  
Amnesic Effect ◽  
In Vivo Experiments ◽  
Toxicological Studies ◽  
Apoptotic Effect ◽  
Pharmaceutical Industries

Scrophulariae Radix (SR) has an important role as a medicinal plant, the roots of which are recorded used to cure fever, swelling, constipation, pharyngitis, laryngitis, neuritis, sore throat, rheumatism, and arthritis in Asia for more than two thousand years. In this paper, the studies published on Scrophularia buergeriana (SB) and Scrophularia ningpoensis (SN) in the latest 20 years were reviewed, and the biological activities of SB and SN were evaluated based on in vitro and in vivo studies. SB presented anti-inflammatory activities, immune-enhancing effects, bone disorder prevention activity, neuroprotective effect, anti-amnesic effect, and anti-allergic effect; SN showed a neuroprotective effect, anti-apoptotic effect, anti-amnesic effect, and anti-depressant effect; and SR exhibited an immune-enhancing effect and cardioprotective effects through in vitro and in vivo experiments. SB and SN are both known to exert neuroprotective and anti-amensice effects. This review investigated their applicability in the nutraceutical, functional foods, and pharmaceutical industries. Further studies, such as toxicological studies and clinical trials, on the efficacy and safety of SR, including SB and SN, need to be conducted.

Two chloroplastic PLGG1 isoforms function together to transport photorespiratory glycolate and glycerate in rice

2021 ◽  
Author(s):  
Lili Cui ◽  
Chuanling Zhang ◽  
Zhichao Li ◽  
Tuxiu Xian ◽  
Limin Wang ◽  
...  
Keyword(s):  
Rice Genome ◽  
Direct Interaction ◽  
Crop Productivity ◽  
Chloroplast Envelope ◽  
Starch Accumulation ◽  
Loss Of Function ◽  
In Planta ◽  
In Vivo Experiments

Abstract The photorespiratory pathway is highly compartmentalized. As such, metabolite shuttles between organelles are critical to ensure efficient photorespiratory carbon flux. Arabidopsis PLGG1 has been reported as a key chloroplastic glycolate/glycerate transporter. Two homologous genes OsPLGG1a and OsPLGG1b have been identified in the rice genome, although their distinct functions and relationships remain unknown. Herein, our analysis of exogenous expression in oocytes and yeast shows that both OsPLGG1a and OsPLGG1b have the ability to transport glycolate and glycerate. Furthermore, we demonstrate in planta, that the perturbation of OsPLGG1a or OsPLGG1b expression leads to extensive accumulation of photorespiratory metabolites, especially glycolate and glycerate. Under ambient CO2 conditions, loss-of-function osplgg1a or osplgg1b mutant plants exhibited significant decreases in photosynthesis efficiency, starch accumulation, plant height, and crop productivity. These morphological defects were almost entirely recovered when the mutant plants were grown under elevated CO2 conditions instead. In contrast to osplgg1a, osplgg1b mutant alleles produced a mild photorespiratory phenotype and had reduced accumulation of photorespiratory metabolites. Subcellular localization analysis showed that OsPLGG1a and OsPLGG1b are located in the inner and outer membranes of the chloroplast envelope, respectively. In vitro and in vivo experiments revealed that OsPLGG1a and OsPLGG1b have a direct interaction. Our results indicate that both OsPLGG1a and OsPLGG1b are chloroplastic glycolate/glycerate transporters required for photorespiratory metabolism and plant growth, and that they may function as a singular complex.

scholarly journals Ethanol extract of Ligustrum lucidum Ait. leaves suppressed hepatocellular carcinoma in vitro and in vivo

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Guoyan Tian ◽  
Jin Chen ◽  
Yan Luo ◽  
Jin Yang ◽  
Tao Gao ◽  
...  
Keyword(s):  
Biological Activities ◽  
Ethanol Extract ◽  
B Cell Lymphoma ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Ligustrum Lucidum ◽  
Specific Pcr ◽  
Cycle Arrest

Abstract Background The present study investigated the pharmacological activity and mechanism of ethanol extract of Ligustrum lucidum Ait. leaves (EEL) on HCC. Methods Cell viability was determined using cell counting kit-8 (CCK-8) assay. The effects of EEL on cellular biological activities were analyzed by flow cytometry (FCM), cell wound scratch assay and transwell assay. The expression levels of related mRNA and protein were determined by performing quantitative real-time PCR (qRT-PCR), Western blotting assay and immunocytochemistry. Methylation-specific PCR (MSP) was carried out to investigate the possible mechanism underlying the DNA methylation of PTEN. Results EEL showed cytotoxicity to both Bel-7402 and Huh-7 cell lines. We also found that EEL enhanced the apoptosis of Bel-7402 and Huh-7 cells by regulating the expressions of Bcl-2 associated X (Bax), B cell lymphoma 2 (Bcl-2) and Cytochrome-C and the activity of caspase-3 and therefore promoted cell cycle arrest. Moreover, EEL also suppressed cell migration and invasion. EEL increased the expression of tissue inhibitor of metalloproteinases 2 (TIMP2) but decreased the expressions of matrix metalloproteinase2 (MMP2) and MMP9. Furthermore, EEL inhibited the phosphorylation of PI3K/Akt pathway. MSP results showed that EEL promoted the demethylation of PTEN, suggesting that the inactivation of PI3K/Akt may be related to DNA de-methylation of PTEN. In addition, EEL inhibited the tumor growth of HCC in vivo. Conclusions EEL exerted anti-tumor effect on HCC in vitro and in vivo. EEL mediated by the inhibition of PI3K/Akt may be closely related to DNA de-methylation of PTEN. Thus, EEL could be used as a potential anti-cancer therapeutic agent of HCC.

scholarly journals Review of Medicinal uses, Phytochemistry and Biological Activities of Antidesma laciniatum and A. membranaceum -

2020 ◽  
Vol 10 (5) ◽  
pp. 257-263
Author(s):  
Alfred Maroyi
Keyword(s):  
Biological Activities ◽  
Clinical Effectiveness ◽  
Extensive Literature ◽  
Medicinal Uses ◽  
Traditional Medicines ◽  
In Vivo Experiments ◽  
Cytotoxicity Activities ◽  
The University

Antidesma laciniatum and A. membranaceum are small trees used as traditional medicines in tropical Africa. This extensive literature review synthesizes the information currently available on the medicinal uses, phytochemistry and biological activities of A. laciniatum and A. membranaceum. The university library and electronic search engines such as Google Scholar, Scopus, Web of Science, ScienceDirect, and PubMed were searched for pertinent information on the medicinal uses, phytochemistry, and biological activities of A. laciniatum and A. membranaceum. Traditionally, the species have been used as aphrodisiac, and traditional medicine for cough, kwashiorkor, mouth ulcers, pneumonia, prevent miscarriage, snakebites, stomachache and wounds. Various phytochemicals such as essential oils, isoflavonoid glycosides, phytosterols, benzopyranones, lignin glucosides, megastigmane, phenolics, steroids, squalene, terpenoids, triterpenoids, and tetrahydroisoquinoline alkaloids have been isolated from A. laciniatum and A. membranaceum. In vitro studies have confirmed the biological activities of A. laciniatum and A. membranaceum which, include antimicrobial, antioxidant, antiplasmodial, antitrypanosomal, leishmanicidal, molluscicidal and cytotoxicity activities. More pharmacological studies including phytochemical, toxicological, in vitro and in vivo experiments are needed to provide evidence for the clinical effectiveness of remedies prepared from the species.

scholarly journals The Regulatory Effect of MicroRNA-101-3p on Disc Degeneration by the STC1/VEGF/MAPK Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Juehan Wang ◽  
Leizhen Huang ◽  
Xi Yang ◽  
Ce Zhu ◽  
Yong Huang ◽  
...  
Keyword(s):  
Disc Degeneration ◽  
Mapk Pathway ◽  
Expression Level ◽  
Regulatory Effect ◽  
In Vivo Experiments ◽  
Novel Mirna ◽  
Pathway Expression ◽  
Endothelial Growth Factor

Aims. Accumulating evidence reported that the microRNA (miRNA) took an important role in intervertebral disc degeneration (IDD). In this study, we revealed a novel miRNA regulatory mechanism in IDD. Main Methods. The miRNA microarray analyses of human degenerated and normal disc samples were employed to screen out the target miRNA. In vitro and in vivo experiments were conducted to verify the regulatory effect of miR-101-3p. Key Findings. The expression level of miR-101-3p was significantly decreased in the degenerated disc samples which were confirmed by qRT-PCR. Moreover, the miR-101-3p expression level was changed dynamically according to the disc degeneration grade. Upregulation of miR-101-3p expression level inhibited cell apoptosis. Furthermore, stanniocalcin-1 (STC1) was selected to be the target gene of miR-101-3p according to the bioinformatic algorithms. Mechanically, upregulation of miR-101-3p significantly decreased the expression of STC1, vascular endothelial growth factor (VEGF), and MAPK pathway expression levels. Therapeutically, in vivo experiment on IDD rat model illustrated that agomir-101-3p could effectively suspend IDD. Significance. Our findings demonstrated that miR-101-3p alleviated IDD process through the STC1/VEGF/MAPK pathway.

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