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

  • Authors:
    • Guodong Lian
    • Leping Li
    • Yulong Shi
    • Changqing Jing
    • Jinglei Liu
    • Xiaobo Guo
    • Qingqing Zhang
    • Tianyu Dai
    • Fei Ye
    • Yanyan Wang
    • Man Chen
  • View Affiliations / Copyright

    Affiliations: 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, Clinical Medical College of Jining Medical University, Jining, Shandong 272067, P.R. China, Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA, Biological Engineering School of Dalian Polytechnic University, Dalian, Liaoning 116034, P.R. China, Department of Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China
    Copyright: © Lian et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 804-814
    |
    Published online on: January 25, 2018
       https://doi.org/10.3892/ijo.2018.4255
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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.
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Copy and paste a formatted citation
Spandidos Publications style
Lian G, Li L, Shi Y, Jing C, Liu J, Guo X, Zhang Q, Dai T, Ye F, Wang Y, Wang Y, et al: BI2536, a potent and selective inhibitor of polo-like kinase 1, in combination with cisplatin exerts synergistic effects on gastric cancer cells. Int J Oncol 52: 804-814, 2018.
APA
Lian, G., Li, L., Shi, Y., Jing, C., Liu, J., Guo, X. ... Chen, M. (2018). BI2536, a potent and selective inhibitor of polo-like kinase 1, in combination with cisplatin exerts synergistic effects on gastric cancer cells. International Journal of Oncology, 52, 804-814. https://doi.org/10.3892/ijo.2018.4255
MLA
Lian, G., Li, L., Shi, Y., Jing, C., Liu, J., Guo, X., Zhang, Q., Dai, T., Ye, F., Wang, Y., Chen, M."BI2536, a potent and selective inhibitor of polo-like kinase 1, in combination with cisplatin exerts synergistic effects on gastric cancer cells". International Journal of Oncology 52.3 (2018): 804-814.
Chicago
Lian, G., Li, L., Shi, Y., Jing, C., Liu, J., Guo, X., Zhang, Q., Dai, T., Ye, F., Wang, Y., Chen, M."BI2536, a potent and selective inhibitor of polo-like kinase 1, in combination with cisplatin exerts synergistic effects on gastric cancer cells". International Journal of Oncology 52, no. 3 (2018): 804-814. https://doi.org/10.3892/ijo.2018.4255
Copy and paste a formatted citation
x
Spandidos Publications style
Lian G, Li L, Shi Y, Jing C, Liu J, Guo X, Zhang Q, Dai T, Ye F, Wang Y, Wang Y, et al: BI2536, a potent and selective inhibitor of polo-like kinase 1, in combination with cisplatin exerts synergistic effects on gastric cancer cells. Int J Oncol 52: 804-814, 2018.
APA
Lian, G., Li, L., Shi, Y., Jing, C., Liu, J., Guo, X. ... Chen, M. (2018). BI2536, a potent and selective inhibitor of polo-like kinase 1, in combination with cisplatin exerts synergistic effects on gastric cancer cells. International Journal of Oncology, 52, 804-814. https://doi.org/10.3892/ijo.2018.4255
MLA
Lian, G., Li, L., Shi, Y., Jing, C., Liu, J., Guo, X., Zhang, Q., Dai, T., Ye, F., Wang, Y., Chen, M."BI2536, a potent and selective inhibitor of polo-like kinase 1, in combination with cisplatin exerts synergistic effects on gastric cancer cells". International Journal of Oncology 52.3 (2018): 804-814.
Chicago
Lian, G., Li, L., Shi, Y., Jing, C., Liu, J., Guo, X., Zhang, Q., Dai, T., Ye, F., Wang, Y., Chen, M."BI2536, a potent and selective inhibitor of polo-like kinase 1, in combination with cisplatin exerts synergistic effects on gastric cancer cells". International Journal of Oncology 52, no. 3 (2018): 804-814. https://doi.org/10.3892/ijo.2018.4255
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