Laboratory of Pharmacogenetics, Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza, Brazil.
Division of Chemical Biology and Medicinal Chemistry, University of North Carolina at Chapel Hill, Eshelman School of Pharmacy, United States of America.
Toxicol In Vitro. 2020 Aug;66:104839. doi: 10.1016/j.tiv.2020.104839. Epub 2020 Mar 31.
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 (p38α) 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 p38α 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.
胃癌一直被认为是最严重的癌症类型之一，因为它在晚期被诊断出来，目前处于转移阶段。因此，挑战在于找到一个生物标志物和药理学靶点，以帮助应对这一全球性的健康问题。在这方面，丝裂原活化蛋白激酶（MAPK）信号通路已成为几种癌症研究的重要目标。因此，我们评估了 MAPK14（p38α）抑制剂 SB-245392 在细胞增殖、细胞死亡和细胞迁移等细胞过程中的作用，以及 MAPK14 基因是否可以成为胃癌模型中的潜在生物标志物。结果清楚地表明，p38α 抑制显著损害细胞增殖，诱导适度凋亡并强烈抑制胃癌细胞（AGP-01）的迁移。基因表达分析显示，SB-245392 处理后 c-MYC 水平降低，TP53 水平升高。此外，在 TCGA 数据库中，与正常样本相比，胃癌样本中 MAPK14 水平较高，尤其是在晚期（3 期和 4 期），这与患者的低生存率显著相关。总之，MAPK14 可能是晚期胃癌的潜在生物标志物和药理学靶点，可以提高患者的生存率。
