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Kinase inhibitor screening reveals aurora-a kinase is a potential therapeutic and prognostic biomarker of gastric cancer
- Source :
- Journal of cellular biochemistryREFERENCES. 122(10)
- Publication Year :
- 2021
-
Abstract
- Gastric cancer is one of the most common and deadly types of cancer in the world, and poor prognosis with treatment failure is widely reported in the literature. In this context, kinases have been considered a relevant choice for targeted therapy in gastric cancer. Here, we explore the antiproliferative and antimigratory effects of the AURKA inhibitor and the prognostic and therapeutic value as a biomarker of gastric cancer. A total of 145 kinase inhibitors were screened to evaluate the cytotoxic or cytostatic effects in the gastric cancer cell line. Using the Alamar Blue assay, flow cytometry, quantitative polymerase chain reaction, and observation of caspase 3/7 activity and cell migration, we investigated the antiproliferative, proapoptotic, and antimigratory effects of the AURKA inhibitor. Moreover, AURKA overexpression was evaluated in the gastric cell lines and the gastric tumor tissue. Out of the 145 inhibitors, two presented the highest antiproliferative effect. Both molecules can induce apoptosis by the caspases 3/7 pathway in addition to inhibiting cancer cell migration, mainly the AURKA inhibitor. Moreover, molecular docking analysis revealed that GW779439X interacts in the active site of the AURKA enzyme with similar energy as a well-described inhibitor. Our study identified AURKA overexpression in the gastric cancer cell line and gastric tumor tissue, revealing that its overexpression in patients with cancer is correlated with low survival. Therefore, it is feasible to suggest AURKA as a potential marker of gastric cancer, besides providing robust information for diagnosis and estimated survival of patients. AURKA can be considered a new molecular target used in the prognosis and therapy of gastric cancer.
- Subjects :
- 0301 basic medicine
Adult
Male
medicine.medical_treatment
Aurora A kinase
Caspase 3
Context (language use)
Antineoplastic Agents
Apoptosis
Biochemistry
Targeted therapy
03 medical and health sciences
0302 clinical medicine
Stomach Neoplasms
Cell Line, Tumor
medicine
Humans
Molecular Biology
Protein Kinase Inhibitors
Aged
Aurora Kinase A
Aged, 80 and over
Kinase
business.industry
Cancer
Cell Biology
Middle Aged
medicine.disease
Prognosis
High-Throughput Screening Assays
Molecular Docking Simulation
Pyridazines
Survival Rate
030104 developmental biology
Real-time polymerase chain reaction
030220 oncology & carcinogenesis
Cancer research
Pyrazoles
Female
Drug Screening Assays, Antitumor
business
Subjects
Details
- ISSN :
- 10974644
- Volume :
- 122
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Journal of cellular biochemistryREFERENCES
- Accession number :
- edsair.doi.dedup.....b2c3a0d3de6a3998d710611aeef39ebb