Akt inhibitor MK-2206 enhances the effect of cisplatin in gastric cancer cells

  • Authors:
    • Kaixiong Tao
    • Yuping Yin
    • Qian Shen
    • Ying Chen
    • Ruidong Li
    • Weilong Chang
    • Jie Bai
    • Weizhen Liu
    • Liang Shi
    • Peng Zhang
  • View Affiliations

  • Published online on: February 5, 2016     https://doi.org/10.3892/br.2016.594
  • Pages: 365-368
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Abstract

The phosphoinositide 3-kinase/Akt pathway activation commonly occurs in various types of human cancer and has an important role in chemoresistance. Combination of traditional chemotherapy drugs and molecular-targeted agents is a promising strategy for cancer therapy, which has shown enhanced cytotoxicity and lower drug resistance. The present study found that the Akt inhibitor, MK-2206, can increase the effect of cisplatin in the gastric cancer cell line AGS, which has higher Akt phosphorylation, but exhibited a poor combination effect in MKN-45 and MGC-803 cells, which have limited Akt activation. The MTT assay demonstrated that sequential treatment of cisplatin, followed by the Akt inhibitor, MK-2206, caused a synergistic effect of proliferation inhibition, and the apoptosis assay by propidium iodide/fluorescein isothiocyanate staining also showed that combination treatment induced more apoptosis compared to the monotherapy groups. Using western blot analysis, MK-2206 was shown to significantly suppress the phosphorylation of Akt (Ser473), however, the expression of total Akt remained the same, and the combination treatment also increased the expression of cleaved poly adenosine diphosphate ribose polymerase, which contributed to apoptosis.
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March-2016
Volume 4 Issue 3

Print ISSN: 2049-9434
Online ISSN:2049-9442

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Spandidos Publications style
Tao K, Yin Y, Shen Q, Chen Y, Li R, Chang W, Bai J, Liu W, Shi L, Zhang P, Zhang P, et al: Akt inhibitor MK-2206 enhances the effect of cisplatin in gastric cancer cells. Biomed Rep 4: 365-368, 2016
APA
Tao, K., Yin, Y., Shen, Q., Chen, Y., Li, R., Chang, W. ... Zhang, P. (2016). Akt inhibitor MK-2206 enhances the effect of cisplatin in gastric cancer cells. Biomedical Reports, 4, 365-368. https://doi.org/10.3892/br.2016.594
MLA
Tao, K., Yin, Y., Shen, Q., Chen, Y., Li, R., Chang, W., Bai, J., Liu, W., Shi, L., Zhang, P."Akt inhibitor MK-2206 enhances the effect of cisplatin in gastric cancer cells". Biomedical Reports 4.3 (2016): 365-368.
Chicago
Tao, K., Yin, Y., Shen, Q., Chen, Y., Li, R., Chang, W., Bai, J., Liu, W., Shi, L., Zhang, P."Akt inhibitor MK-2206 enhances the effect of cisplatin in gastric cancer cells". Biomedical Reports 4, no. 3 (2016): 365-368. https://doi.org/10.3892/br.2016.594