Cisplatin‐resistant cancer cells are sensitive to Aurora kinase A inhibition by alisertib

De novo and acquired resistance to platinum therapy such as cisplatin (CDDP) is a clinical challenge in gastric cancer treatment. Aberrant expression and activation of aurora kinase A (AURKA) and eukaryotic translation initiation factor 4E (eIF4E) are detected in several cancer types. Herein, we inv...

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Bibliographic Details
Published in:Molecular oncology 2017-08, Vol.11 (8), p.981-995
Main Authors: Wang, Lihong, Arras, Janet, Katsha, Ahmed, Hamdan, Saif, Belkhiri, Abbes, Ecsedy, Jeffrey, El‐Rifai, Wael
Format: Article
Language:English
Subjects:
alisertib
Analysis
Animals
Aurora kinase
Aurora Kinase A - antagonists & inhibitors
Aurora Kinase A - metabolism
Azepines - pharmacology
Cancer
Cancer cells
Cancer therapies
Care and treatment
Cell culture
Cell cycle
Cell Line, Tumor
Cisplatin
Cisplatin - pharmacology
Cloning
Drug resistance
Drug Resistance, Neoplasm - drug effects
eIF4E
Esophagus
Female
Gastric cancer
Genetic translation
HDM2
Humans
Initiation factor eIF-4E
Kinases
Laboratories
Melanoma
Mice
Mice, Nude
MLN8237
MYC
Myc protein
Neoplasm Proteins - antagonists & inhibitors
Neoplasm Proteins - metabolism
Neoplasms - drug therapy
Neoplasms - enzymology
Neoplasms - pathology
Ovarian cancer
Phosphorylation
Platinum
Prevention
Proteins
Pyrimidines - pharmacology
Stomach cancer
Studies
Vemurafenib
Xenograft Model Antitumor Assays
Xenografts
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Summary:De novo and acquired resistance to platinum therapy such as cisplatin (CDDP) is a clinical challenge in gastric cancer treatment. Aberrant expression and activation of aurora kinase A (AURKA) and eukaryotic translation initiation factor 4E (eIF4E) are detected in several cancer types. Herein, we investigated the role of AURKA in CDDP resistance in gastric cancer. Western blot analysis demonstrated overexpression of AURKA and phosphorylation of eIF4E in acquired and de novo CDDP‐resistant gastric cancer models. Inhibition of AURKA with MLN8237 (alisertib) alone or in combination with CDDP significantly suppressed viability of CDDP‐resistant cancer cells (P 
ISSN:1574-7891
1878-0261
DOI:10.1002/1878-0261.12066