Role of the eIF4E binding protein 4E-BP1 in regulation of the sensitivity of human pancreatic cancer cells to TRAIL and celastrol-induced apoptosis

2013 ◽  
Vol 105 (9) ◽  
pp. 414-429 ◽  
Author(s):  
Reka Chakravarthy ◽  
Michael J. Clemens ◽  
Grisha Pirianov ◽  
Nectarios Perdios ◽  
Satvinder Mudan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Binding Protein ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells ◽  
Induced Apoptosis

scholarly journals Differential Dependency of Human Pancreatic Cancer Cells on Targeting PTEN via PLK 1 Expression

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 277
Author(s):  
Jungwhoi Lee ◽  
Jungsul Lee ◽  
Woogwang Sim ◽  
Jae-Hoon Kim
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Intracellular Signaling ◽  
Biomarker Discovery ◽  
Human Pancreatic Cancer ◽  
Normal Tissues ◽  
Pancreatic Cancer Cells ◽  
Prognostic Implications ◽  
Plk1 Expression

Even though the tumour suppressive role of PTEN is well-known, its prognostic implications are ambiguous. The objective of this study was to further explore the function of PTEN expression in human pancreatic cancer. The expression of PTEN has been dominant in various human cancers including pancreatic cancer when compared with their matched normal tissues. The pancreatic cancer cells have been divided into PTEN blockade-susceptible and PTEN blockade-impassible groups dependent on targeting PTEN by altering intracellular signaling. The expression of PTEN has led to varying clinical outcomes of pancreatic cancer based on GEO Series (GSE) data analysis and Liptak’s z analysis. Differential dependency to PTEN blockade has been ascertained based on the expression of polo-like kinase1 PLK1 in pancreatic cancer cells. The prognostic value of PTEN also depends on PLK1 expression in pancreatic cancer. Collectively, the present study provides a rationale for targeting PTEN as a promising therapeutic strategy dependent on PLK1 expressions using a companion biomarker discovery platform.

Possible role of autophagy inhibition in hypoxia-induced chemoresistance of pancreatic cancer cells.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 224-224 ◽  
Author(s):  
Yoon Ho Ko ◽  
Young-Seok Cho ◽  
Hye Sung Won ◽  
Eun Kyoung Jeon ◽  
Young Seon Hong
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Western Blotting ◽  
Pancreatic Cancer Cell Line ◽  
Cancer Cell Line ◽  
Hypoxic Condition ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells ◽  
Autophagy Inhibition

224 Background: Autophagy is a catabolic process and provides metabolic support for the cell by degradation of intracellular macromolecules. Various types of stress, including hypoxia, activate autophagy. Recent studies have suggested that hypoxia has been shown to associate with resistance to chemotherapy and radiation therapy and hence poor prognosis in pancreatic cancer. This study investigated the role of autophagy in the treatment of pancreatic cancer with gemcitabine under hypoxic condition. Methods: To evaluate the role of autophagy inhibition in hypoxia-induced chemoresistance, BxPC-3 human pancreatic cancer cell line was used under normoxic and hypoxic conditions.We evaluated the extent of LC3-II, as an autophagosome marker, induced by gemcitabine, by western blotting to measure the hypoxia- or chemotherapy- induced autophagy. We then examined the effects of gemcitabine on induction of apoptosis under normoxic and hypoxic conditions. Next, to determine the effect of 3-MA, a known inhibitor of autophagy, on overcoming hypoxia-induced chemoresistance, the MTS assay and flow cytometry were performed. Results: Compared with normoxia, gemcitabine-induced cell death under hypoxia was significantly decreased, as a result of the reduced apoptosis. Western blotting analysis demonstrated that LC3-II was increased under hypoxia, compared with normoxia.However, we found that 3-MA can enhance the growth inhibition and apoptotic effect of gemcitabine, even under hypoxia. These findings mean that autophagy mediates the chemoresistance under hypoxia. Conclusions: Activated autophagy plays a role in hypoxia-induced chemoresistance of pancreatic cancer cells. These findings may have important implications for future therapeutic strategies using gemcitabine against pancreatic cancer.

Effect of PPARδ Agonist on Stearoyl-CoA Desaturase 1 in Human Pancreatic Cancer Cells: Role of MEK/ERK1/2 Pathway

2015 ◽  
Vol 39 (2) ◽  
pp. 123-127 ◽  
Author(s):  
Shima Byagowi ◽  
Taghi Naserpour Farivar ◽  
Reza Najafipour ◽  
Mehdi Sahmani ◽  
Masoud Darabi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells ◽  
Stearoyl Coa Desaturase

Salicylates Inhibit NF-κB Activation and Enhance TNF-α-Induced Apoptosis in Human Pancreatic Cancer Cells

1999 ◽  
Vol 83 (1) ◽  
pp. 56-61 ◽  
Author(s):  
Theodore P. McDade ◽  
Richard A. Perugini ◽  
Frank J. Vittimberga ◽  
Rebecca C. Carrigan ◽  
Mark P. Callery
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells ◽  
Tnf Α ◽  
Induced Apoptosis

GDC-0980-induced apoptosis is enhanced by autophagy inhibition in human pancreatic cancer cells

2014 ◽  
Vol 453 (3) ◽  
pp. 533-538 ◽  
Author(s):  
Jian-ying Tang ◽  
Tu Dai ◽  
Hui Zhang ◽  
Wu-jun Xiong ◽  
Ming-zheng Xu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells ◽  
Induced Apoptosis ◽  
Autophagy Inhibition

scholarly journals Growth Hormone Receptor Inhibition Sensitizes Human Pancreatic Cancer to Chemotherapy Treatments

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1019-A1020
Author(s):  
Reetobrata Basu ◽  
John Joseph Kopchick ◽  
Silvana Duran Ortiz ◽  
Yanrong Qian ◽  
Prateek Kulkarni
Keyword(s):  
Pancreatic Cancer ◽  
Growth Hormone ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Human Pancreatic Cancer ◽  
Drug Efflux ◽  
Pancreatic Cancer Cells

Abstract Human growth hormone (GH) and its cognate growth hormone receptor (GHR) have been established to have a distinct role in promoting the progression of several types of human cancers. We had earlier described a newfound role of the GH-GHR axis in driving chemoresistance in melanoma by upregulating drug efflux by ABC multidrug transporter expression and a phenotype switch by induction of epithelial-to-mesenchymal transition (EMT). Here we present an in-depth analysis of this role of GH-GHR in the highly therapy resistant human pancreatic cancer which has a 5-year survival rate of only 10% in 2020. Using human and mouse pancreatic cancer cells and RNA and protein expression analyses by RT-qPCR, ELISA, and western-blot, we identified that (i) GH upregulates specific ABC-transporter expressions in a drug-context specific manner, (ii) GH upregulates EMT transcription factors, (iii) GH activates specific oncogenic signaling pathways, and (iii) GH action increases cytochrome P450 members involved in hepatic drug metabolism. The GH antagonist, Pegvisomant, significantly inhibited these effects. Additionally, we confirmed the effects of these molecular changes by specific assays. For example, GH increases basement membrane invasion, viability of circulating tumor cells, and drug efflux; while inhibition of GHR by pegvisomant in pancreatic cancer cells reversed this aggressive tumor phenotype and sensitized the tumor cells to chemotherapy. Cell viability assays confirmed a decreased IC50 of gemcitabine, doxorubicin, and erlotinib in pancreatic cancer cells treated with pegvisomant and an increase in IC50 cells treated with GH. We further verified our results using in silico analyses of TCGA datasets for pancreatic cancer - which provided robust confirmation of our experimental findings. Presently we are validating our observation in nude mice with human pancreatic cancer cell xenografts. In conclusion, our in vitro results confirm that GHR antagonism can drastically sensitize human pancreatic cancer cells by blocking mechanisms of drug resistance, thus providing a valuable window for improved efficacy of available chemo- and targeted therapy.

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