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BI2536 是一种有效的、选择性的 Polo 样激酶 1 抑制剂，与顺铂联合使用对胃癌细胞具有协同作用。

BI2536, a potent and selective inhibitor of polo-like kinase 1, in combination with cisplatin exerts synergistic effects on gastric cancer cells.

机构信息

Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.

Statistics and Medical Record Management Section, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.

出版信息

Int J Oncol. 2018 Mar;52(3):804-814. doi: 10.3892/ijo.2018.4255. Epub 2018 Jan 25.

DOI:10.3892/ijo.2018.4255
PMID:29393385
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5807034/
Abstract

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.

摘要

BI2536 是一种高度选择性和有效的 Polo 样激酶 1（PLK1）抑制剂。在这项研究中，我们旨在确定 BI2536 和顺铂是否可以协同抑制胃癌细胞的恶性行为。为此，确定了胃癌细胞中 PLK1 的表达。评估了 BI2536、顺铂以及 BI2536 和顺铂联合对胃癌细胞活力、侵袭、细胞周期停滞和凋亡的影响。此外，还检查了细胞周期调节蛋白的表达。此外，在用 BI2536（IC50）处理 48 小时后，通过蛋白通路阵列分析了 SGC-7901 和 SGC-7901/DDP（顺铂耐药）细胞之间差异表达的蛋白质和富集的信号通路。我们的结果表明，PLK1 在 SGC-7901/DDP（顺铂耐药）胃癌细胞中上调，而在 SGC-7901 细胞中下调。BI2536 增强了顺铂对 SGC-7901 细胞活力和侵袭的抑制作用。BI2536 诱导 SGC-7901 和 SGC-7901/DDP 细胞 G2/M 期停滞。BI2536 促进了 SGC-7901/DDP 细胞对顺铂诱导的细胞凋亡。它还诱导了 SGC-7901 和 SGC-7901/DDP 细胞之间 68 种蛋白质的差异表达，这些差异表达的蛋白质参与了许多细胞功能和信号通路，如细胞死亡、细胞发育、肿瘤发生、细胞周期、DNA 复制/重组/修复、细胞运动以及 Wnt/β-catenin 和丝裂原激活蛋白激酶（MEK）/细胞外信号调节激酶（ERK）/核糖体 S6 激酶 1（RSK1）信号通路。总的来说，我们的研究结果表明，BI2536 和顺铂协同抑制 SGC-7901/DDP（顺铂耐药）胃癌细胞的恶性行为。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed25/5807034/c2c2e67cdc9c/IJO-52-03-0804-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed25/5807034/a5de2e42dbe7/IJO-52-03-0804-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed25/5807034/7e28e34cbc9c/IJO-52-03-0804-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed25/5807034/c24e77a53d2c/IJO-52-03-0804-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed25/5807034/76c1824a7b08/IJO-52-03-0804-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed25/5807034/5f9b7bcd3ab8/IJO-52-03-0804-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed25/5807034/c2c2e67cdc9c/IJO-52-03-0804-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed25/5807034/a5de2e42dbe7/IJO-52-03-0804-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed25/5807034/7e28e34cbc9c/IJO-52-03-0804-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed25/5807034/c24e77a53d2c/IJO-52-03-0804-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed25/5807034/76c1824a7b08/IJO-52-03-0804-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed25/5807034/5f9b7bcd3ab8/IJO-52-03-0804-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed25/5807034/c2c2e67cdc9c/IJO-52-03-0804-g05.jpg

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