Silencing GS Homeobox 2 Alleviates Gemcitabine Resistance in Pancreatic Cancer Cells by Activating SHH/GLI1 Signaling Pathway

2021 ◽  
Author(s):  
Lu Zhuang ◽  
Yao Yao ◽  
Lisi Peng ◽  
Fang Cui ◽  
Cui Chen ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Gemcitabine Resistance ◽  
Pancreatic Cancer Cells

Akt/mTOR signaling pathway is crucial for gemcitabine resistance induced by Annexin II in pancreatic cancer cells

2012 ◽  
Vol 178 (2) ◽  
pp. 758-767 ◽  
Author(s):  
Shingo Kagawa ◽  
Shigetsugu Takano ◽  
Hideyuki Yoshitomi ◽  
Fumio Kimura ◽  
Mamoru Satoh ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Annexin Ii ◽  
Mtor Signaling Pathway ◽  
Gemcitabine Resistance ◽  
Pancreatic Cancer Cells

scholarly journals Selenoprotein P, as a predictor for evaluating gemcitabine resistance in human pancreatic cancer cells

2004 ◽  
Vol 112 (2) ◽  
pp. 184-189 ◽  
Author(s):  
Shin-ichiro Maehara ◽  
Shinji Tanaka ◽  
Mitsuo Shimada ◽  
Ken Shirabe ◽  
Yoshiro Saito ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Human Pancreatic Cancer ◽  
Selenoprotein P ◽  
Gemcitabine Resistance ◽  
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

Gemcitabine induces apoptosis and autophagy via the AMPK/mTOR signaling pathway in pancreatic cancer cells

2018 ◽  
Vol 65 (5) ◽  
pp. 665-671 ◽  
Author(s):  
Jinhui Zhu ◽  
Yan Chen ◽  
Yun Ji ◽  
Yuanquan Yu ◽  
Yun Jin ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Pancreatic Cancer Cells

Brusatol inhibits growth and induces apoptosis in pancreatic cancer cells via JNK/p38 MAPK/NF-κb/Stat3/Bcl-2 signaling pathway

2017 ◽  
Vol 487 (4) ◽  
pp. 820-826 ◽  
Author(s):  
Yukai Xiang ◽  
Wen Ye ◽  
Chaohao Huang ◽  
Bin Lou ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Pancreatic Cancer Cells

scholarly journals m6A Methyltransferase METTL14-Mediated Upregulation of Cytidine Deaminase Promoting Gemcitabine Resistance in Pancreatic Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Congjun Zhang ◽  
Shuangyan Ou ◽  
Yuan Zhou ◽  
Pei Liu ◽  
Peiying Zhang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Western Blotting ◽  
Protein Level ◽  
Cytidine Deaminase ◽  
Critical Role ◽  
Human Pancreatic Cancer ◽  
Gemcitabine Resistance ◽  
Pancreatic Cancer Cells

ObjectivePancreatic cancer is one of the most lethal human malignancies. Gemcitabine is widely used to treat pancreatic cancer, and the resistance to chemotherapy is the major difficulty in treating the disease. N6-methyladenosine (m6A) modification, which regulates RNA splicing, stability, translocation, and translation, plays critical roles in cancer physiological and pathological processes. METTL14, an m6A Lmethyltransferase, was found deregulated in multiple cancer types. However, its role in gemcitabine resistance in pancreatic cancer remains elusive.MethodsThe mRNA and protein level of m6A modification associated genes were assessed by QRT-PCR and western blotting. Then, gemcitabine‐resistant pancreatic cancer cells were established. The growth of pancreatic cancer cells were analyzed using CCK8 assay and colony formation assay. METTL14 was depleted by using shRNA. The binding of p65 on METTL14 promoter was assessed by chromatin immunoprecipitation (ChIP) assay. Protein level of deoxycytidine kinase (DCK) and cytidine deaminase (CDA) was evaluated by western blotting. In vivo experiments were conducted to further confirm the critical role of METTL14 in gemcitabine resistance.ResultsWe found that gemcitabine treatment significantly increased the expression of m6A methyltransferase METTL14, and METTL14 was up-regulated in gemcitabine-resistance human pancreatic cancer cells. Suppression of METTL14 obviously increased the sensitivity of gemcitabine in resistant cells. Moreover, we identified that transcriptional factor p65 targeted the promoter region of METTL14 and up-regulated its expression, which then increased the expression of cytidine deaminase (CDA), an enzyme inactivates gemcitabine. Furthermore, in vivo experiment showed that depletion of METTL14 rescue the response of resistance cell to gemcitabine in a xenograft model.ConclusionOur study suggested that METTL14 is a potential target for chemotherapy resistance in pancreatic cancer.

PTEN regulate angiogenesis through PI3K/Akt/VEGF signaling pathway in human pancreatic cancer cells

2009 ◽  
Vol 331 (1-2) ◽  
pp. 161-171 ◽  
Author(s):  
Jiachi Ma ◽  
Hirozumi Sawai ◽  
Nobuo Ochi ◽  
Yoichi Matsuo ◽  
Donghui Xu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Human Pancreatic Cancer ◽  
Vegf Signaling ◽  
Pancreatic Cancer Cells ◽  
Vegf Signaling Pathway

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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