BI2536, a potent and selective inhibitor of polo-like kinase 1, in combination with cisplatin exerts synergistic effects on gastric cancer cells.
BI2536, a potent and selective inhibitor of polo-like kinase 1, in combination with cisplatin exerts synergistic effects on gastric cancer cells.
复制标题
BI2536是一种有效的、选择性的polo样激酶1抑制剂，与顺铂联用对胃癌细胞发挥协同作用
DOI：
10.3892/ijo.2018.4255
复制
发表时间：
2018-03
影响因子：
5.2
通讯作者：
Chen M
中科院分区：
文献类型：
--
作者：
Lian G;Li L;Shi Y;Jing C;Liu J;Guo X;Zhang Q;Dai T;Ye F;Wang Y;Chen M
BI 2536是一种高度选择性且有效的Polo样激酶1（PLK 1）抑制剂。在这项研究中，我们的目的是确定是否BI 2536和顺铂可以协同抑制胃癌细胞的恶性行为。为此，测定胃癌细胞中PLK 1的表达。评估了BI 2536、顺铂以及BI 2536和顺铂的组合对胃癌细胞活力、侵袭、细胞周期阻滞和凋亡的影响。此外，检测细胞周期调节蛋白的表达。采用蛋白质通路芯片分析BI 2536处理SGC-7901和SGC-7901/DDP（顺铂耐药）细胞48 h后差异表达的蛋白质及富集的信号通路（IC 50）。我们的研究结果显示，PLK 1在SGC-7901/DDP（顺铂耐药）胃癌细胞中的表达较SGC-7901细胞上调。BI 2536可增强顺铂对胃癌SGC-7901细胞活力和侵袭力的抑制作用。BI 2536可诱导SGC-7901和SGC-7901/DDP细胞发生G2/M期阻滞。BI 2536可促进顺铂诱导的胃癌SGC-7901/DDP细胞凋亡。结果表明，胃癌细胞株SGC-7901和SGC-7901/DDP细胞中存在68个蛋白质的差异表达，这些差异表达的蛋白质参与了细胞死亡、细胞发育、肿瘤发生、细胞周期、DNA复制/重组/修复、细胞运动、Wnt/β-catenin和丝裂原活化蛋白激酶（MEK）/细胞外信号调节激酶（ERK）/核糖体S6激酶1（RSK 1）信号通路。总体而言，我们的研究结果表明，BI 2536和顺铂协同抑制SGC-7901/DDP（顺铂耐药）胃癌细胞的恶性行为。
BI2536 is a highly selective and potent inhibitor of polo-like kinase 1 (PLK1). In this study, we aimed to determine whether BI2536 and cisplatin can synergistically inhibit the malignant behavior of gastric cancer cells. For this purpose, the expression of PLK1 in gastric cancer cells was determined. The effects of BI2536, cisplatin, and the combination of BI2536 and cisplatin on gastric cancer cell viability, invasion, cell cycle arrest and apoptosis were assessed. Furthermore, the expression of cell cycle-regulated proteins was examined. Moreover, the differentially expressed proteins between the SGC-7901 and SGC-7901/DDP (cisplatin-resistant) cells, and the enriched signaling pathways were analyzed by protein pathway array following treatment with BI2536 (IC50) for 48 h. Our results revealed that PLK1 was upregulated in the SGC-7901/DDP (cisplatin-resistant) gastric cancer cells compared with the SGC-7901 cells. BI2536 enhanced the inhibitory effect of cisplatin on SGC-7901 cell viability and invasion. BI2536 induced G2/M arrest in SGC-7901 and SGC-7901/DDP cells. BI2536 promoted cisplatin-induced gastric cancer SGC-7901/DDP cell apoptosis. It also induced the differential expression of 68 proteins between the SGC-7901 and SGC-7901/DDP cells, and these differentially expressed proteins were involved in a number of cellular functions and signaling pathways, such as cell death, cell development, tumorigenesis, the cell cycle, DNA duplication/recombination/repair, cellular movement, and the Wnt/β-catenin and mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK)/ribosomal S6 kinase 1 (RSK1) signaling pathways. On the whole, our findings suggest that BI2536 and cisplatin synergistically inhibit the malignant behavior of SGC-7901/DDP (cisplatin-resistant) gastric cancer cells.
登录
查看更多内容
影响因子：
9
作者：
通讯作者：
--
影响因子：
9.2
作者：
Lenart, Peter;Petronczki, Mark;Peters, Jan-Michael
通讯作者：
Peters, Jan-Michael
影响因子：
4.3
作者：
Orditura, Michele;Galizia, Gennaro;De Vita, Ferdinando
通讯作者：
De Vita, Ferdinando
影响因子：
5.2
作者：
Kim, Soo-A;Kwon, Seong-Min;Ahn, Sang-Gun
通讯作者：
Ahn, Sang-Gun
影响因子：
3.7
作者：
de Martel, Catherine;Forman, David;Plummer, Martyn
通讯作者：
Plummer, Martyn