TY - JOUR
T1 - BI2536, a potent and selective inhibitor of polo-like kinase 1, in combination with cisplatin exerts synergistic effects on gastric cancer cells
AU - Lian, Guodong
AU - Li, Leping
AU - Shi, Yulong
AU - Jing, Changqing
AU - Liu, Jinglei
AU - Guo, Xiaobo
AU - Zhang, Qingqing
AU - Dai, Tianyu
AU - Ye, Fei
AU - Wang, Yanyan
AU - Chen, Man
PY - 2018/3
Y1 - 2018/3
N2 - 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.
AB - 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.
KW - Cisplatin
KW - Gastric cancer
KW - Polo-like kinase 1 inhibitor
KW - Protein pathway array
KW - Synergistic
UR - https://www.scopus.com/pages/publications/85041582372
U2 - 10.3892/ijo.2018.4255
DO - 10.3892/ijo.2018.4255
M3 - Article
C2 - 29393385
AN - SCOPUS:85041582372
SN - 1019-6439
VL - 52
SP - 804
EP - 814
JO - International Journal of Oncology
JF - International Journal of Oncology
IS - 3
ER -