2019
DOI: 10.1016/j.jbior.2019.03.002
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Effects of the MDM-2 inhibitor Nutlin-3a on PDAC cells containing and lacking WT-TP53 on sensitivity to chemotherapy, signal transduction inhibitors and nutraceuticals

Abstract: Mutations at the TP53 gene are readily detected (approximately 50-75%) in pancreatic ductal adenocarcinoma (PDAC) patients. TP53 was previously thought to be a difficult target as it is often mutated, deleted or inactivated on both chromosomes in certain cancers. In the following study, the effects of restoration of wild-type (WT) TP53 activity on the sensitivities of MIA-PaCa-2 pancreatic cancer cells to the MDM2 inhibitor nutlin-3a in combination with chemotherapy, targeted therapy, as well as, nutraceutical… Show more

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Cited by 10 publications
(7 citation statements)
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References 105 publications
(144 reference statements)
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“…The MIA-PaCa-2+WT-TP53 cells were more sensitive to the chemotherapeutic drugs compared to MIA-PaCa-2+pLXSN cells (Supplementary Figure 1). Similar results have been reported by earlier studies [23,[31][32][33]. The above results authenticate the physiological effects of expressing different forms of TP53 and associated cell signaling.…”
Section: Profiling Of Tumor Promoting and Suppressor Proteins In Response To Expression Of Wild-type Tp53 In Mia-paca-2 Cellssupporting
confidence: 91%
See 1 more Smart Citation
“…The MIA-PaCa-2+WT-TP53 cells were more sensitive to the chemotherapeutic drugs compared to MIA-PaCa-2+pLXSN cells (Supplementary Figure 1). Similar results have been reported by earlier studies [23,[31][32][33]. The above results authenticate the physiological effects of expressing different forms of TP53 and associated cell signaling.…”
Section: Profiling Of Tumor Promoting and Suppressor Proteins In Response To Expression Of Wild-type Tp53 In Mia-paca-2 Cellssupporting
confidence: 91%
“…MIA-PaCa-2 cells were purchased from the ATCC (Rockville, MD, USA). Cells were cultured in medium containing 5% fetal bovine serum (FBS) purchased from (Atlanta Biologicals, Atlanta, GA, USA) as described in [33]. Tissue culture medium (Dulbecco's modified Eagles medium, DMEM), antibiotics containing l-glutamine and trypsin were obtained from Invitrogen (Carlsbad, CA, USA).…”
Section: Cellsmentioning
confidence: 99%
“…Two important kinase cascades are the Raf/MEK/ERK and PI3K/PTEN/Akt/mTORC1 pathways. They are often involved in regulation of cell growth and their aberrant regulation is often implicated in cancer [ 45 47 ]. Restoration of WT-TP53 activity in MIA-PaCa-2 cells increased the sensitivity to the MEK1 inhibitor PD0325901 3.3-fold.…”
Section: Resultsmentioning
confidence: 99%
“…The percentage of positive cells was defined as follows: 0, <5%; 1, 5-25%; 2, 26-50%; and 3, 51-100%. MEF2C and TCF4 staining scores were classified as low expression (0-1) or high expression (2)(3)(4)(5)(6).…”
Section: Bioinformatics Analyses and Luciferase Reporter Assaysmentioning
confidence: 99%
“…Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and lethal malignant tumor encountered worldwide (1)(2)(3)(4)(5). Although extensive research studies have investigated diagnostic biomarkers for PDAC, detailed analyses of the underlying molecular mechanisms are still needed for the development of targeted therapies (1).…”
Section: Introductionmentioning
confidence: 99%