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UNBS5162 作为一种新型萘酰亚胺,通过 AKT/ERK 信号通路在人胃癌细胞行为中具有疗效。

UNBS5162 as a novel naphthalimide holds efficacy in human gastric carcinoma cell behaviors mediated by AKT/ERK signaling pathway.

机构信息

a Department of General Surgery , The Second Affiliated Hospital of Mudanjiang Medical University , Mudanjiang , China.

b Department of Medical Records Management , The Second Affiliated Hospital of Mudanjiang Medical University , Mudanjiang , China.

出版信息

Drug Dev Ind Pharm. 2019 Aug;45(8):1306-1312. doi: 10.1080/03639045.2019.1607870. Epub 2019 May 24.

Abstract

Studies have determined that UNBS5162, recognized as a new naphthalimide, holds inhibitory effects in prostate and breast tumors; however, its functional implication on gastric carcinoma is currently undetermined. Based on this, this study designed to assess the functional role of it on human gastric carcinoma and underlying mechanism of action. Cell counting kit-8 (CCK-8) assay, transwell assay, and flow cytometry were used to assess capabilities of SGC-7901 cell proliferation, invasion/migration, and apoptosis, respectively. Moreover, western blot was performed to determine the relative expression of protein related to autophagy and protein kinase B (AKT)/extracellular regulated protein kinases (ERK) signaling pathway. We found SGC-7901 cells proliferation, invasion, and migration were significantly inhibited after treatment of UNBS5162. Moreover, the expression levels of anti-apoptotic protein Bcl-2 decreased while the expression of pro-apoptotic protein active caspase 3 and Bax increased concurrently after UNBS5162 stimulation. Further, upregulated LC3 II/I and Beclin-1 and downregulated P62 were induced by UNBS5162 addition. Mechanically, the ratios of phosphorylated-(p-)AKT/AKT, p-mammalian target of rapamycin (mTOR)/mTOR, and p-ERK/ERK were hampered by UNBS5162 application. UNBS5162 could restrain gastric carcinoma cell proliferation, invasion, and migration, which maybe induced by enhancement of apoptosis, autophagy manipulated through AKT/ERK signaling pathway.

摘要

研究表明,被认定为新型萘二酰亚胺的 UNBS5162 对前列腺和乳腺癌肿瘤具有抑制作用;然而,其对胃癌的功能影响目前尚不清楚。基于此,本研究旨在评估其对人胃癌的功能作用及其作用机制。细胞计数试剂盒-8(CCK-8)检测、Transwell 检测和流式细胞术分别用于评估 SGC-7901 细胞增殖、侵袭/迁移和凋亡能力。此外,Western blot 用于确定与自噬和蛋白激酶 B(AKT)/细胞外调节蛋白激酶(ERK)信号通路相关的蛋白的相对表达。我们发现,UNBS5162 处理后 SGC-7901 细胞的增殖、侵袭和迁移能力显著受到抑制。此外,UNBS5162 刺激后抗凋亡蛋白 Bcl-2 的表达水平降低,而促凋亡蛋白活性 caspase 3 和 Bax 的表达水平升高。进一步研究发现,UNBS5162 增加了 LC3 II/I 和 Beclin-1 的表达,同时降低了 P62 的表达。机制上,UNBS5162 应用抑制了磷酸化-AKT/AKT(p-AKT/AKT)、磷酸化-哺乳动物雷帕霉素靶蛋白(mTOR)/mTOR(p-mTOR/mTOR)和磷酸化-细胞外调节蛋白激酶(ERK)/ERK(p-ERK/ERK)的比值。UNBS5162 可抑制胃癌细胞的增殖、侵袭和迁移,其机制可能是通过 AKT/ERK 信号通路增强细胞凋亡和自噬。

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