title: Akt inhibitor MK-2206 enhances the effect of cisplatin in gastric cancer cells.
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.
authors.affiliation: Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Kaixiong
authors.initials: K
authors.lastname: Tao
authors.affiliation: Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Ruidong
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Weilong
authors.initials: W
authors.lastname: Chang
authors.affiliation: Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Bai
authors.affiliation: Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Weizhen
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
keywords: MK-2206; cisplatin; gastric cancer; phosphoinositide 3-kinase/Akt pathway