MAPK14 (p38α) inhibition effects against metastatic gastric cancer cells: A potential biomarker and pharmacological target

被引：27
作者：
Mesquita, Felipe Pantoja [1 ]
Moreira-Nunes, Caroline Aquino [1 ]
da Silva, Emerson Lucena [1 ]
Lima, Luina Benevides [1 ]
Daniel, Julio Paulino [1 ]
Zuerker, William J. [2 ]
Brayner, Mirna [1 ]
Amaral de Moraes, Maria Elisabete [1 ]
Montenegro, Raquel Carvalho [1 ]
机构：
[1] Univ Fed Ceara, Drug Res & Dev Ctr NPDM, Lab Pharmacogenet, St Cel Nunes Melo 1000, Fortaleza, Ceara, Brazil
[2] Univ N Carolina, Div Chem Biol & Med Chem, Eshelman Sch Pharm, Chapel Hill, NC 27515 USA
来源：
TOXICOLOGY IN VITRO | 2020年 / 66卷
关键词：
Metastatic gastric cancer; Kinase inhibition; MAPK14; Drug target; Biomarker; P38; MAPK; BREAST-CANCER; UP-REGULATION; KAPPA-B; MIGRATION; PROLIFERATION; INVASION; EXPRESSION; PATHWAYS; SPREAD;
D O I：
10.1016/j.tiv.2020.104839
中图分类号：
R99 [毒物学（毒理学）];
学科分类号：
100405 ;
摘要：
Gastric cancer has been considering one of the worst cancer types since it is diagnosed in advanced stages, currently in the metastatic stage. Therefore, the challenge is to find out a biomarker and a pharmacology target that would help face this worldwide health issue. In this sense, the mitogen-activated protein kinase (MAPK) signaling pathway has become an important aim of the studies in several cancers. Therefore, we evaluated the role of MAPK14 (p38 alpha) inhibitor SB-245392 in the cellular process, such as proliferation, cell death, and cell migration, and whether MAPK14 gene could be a potential biomarker in gastric cancer models. The results clearly suggest that p38 alpha inhibition significantly impairs the cell proliferation, induces modest apoptosis and strongly inhibits cell migration of gastric cancer cell (AGP-01). Gene expression analysis showed that c-MYC level was decreased and TP53 was increased after SB-245392 treatment. Furthermore, MAPK14 was found in high levels in gastric cancer samples compared to normal samples in the TCGA database, especially in advanced stages (stage 3 and 4), which is significantly associated with low rate survival of the patients. In conclusion, the MAPK14 could be a potential biomarker for advanced gastric cancer as well as a pharmacological target, which could improve the survival rate of patients.
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页数：8
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