title: MK-2206 co-treatment with 5-fluorouracil or doxorubicin enhances chemosensitivity and apoptosis in gastric cancer by attenuation of Akt phosphorylation.
abstract: The anticancer effect of MK-2206, an Akt inhibitor, has been explored in some types of cancers, but its effect on gastric cancer is unclear. In this study, we aimed to investigate its anticancer effect in gastric cancer cells. Cell viability and colony formation assays showed that MK-2206 effectively inhibited the proliferation of SGC-7901 and MKN45 cells. The 50% inhibitory concentration values after 24, 48, and 72 hours' treatment were 22.92, 13.68, and 8.55 μM in SGC-7901 cells and 19.21, 13.10, and 9.11 μM in MKN45 cells, respectively. Treatment with MK-2206 induced apoptosis in SGC-7901 cells as indicated by flow cytometry assay. The combination indexes of MK-2206 and doxorubicin were 0.59 in SGC-7901 cells and 0.57 in MKN45 cells, whereas for 5-fluorouracil (5-FU) the indexes were 0.17 in SGC-7901 cells and 0.73 in MKN45 cells, indicating that MK-2206 could work synergistically with doxorubicin or 5-FU to inhibit cell growth. Furthermore, a small dose (1 μM) of MK-2206 co-treatment with doxorubicin or 5-FU was sufficient for complete inhibition of chemotherapeutic alteration of phosphorylated Akt expression and significant enhancement of pro-apoptosis effect through the activation of caspase pathway. Therefore, MK-2206 effectively inhibits gastric cancer cell growth by attenuation of Akt phosphorylation and synergistically enhances the antitumor effect of doxorubicin and 5-FU via caspase-dependent apoptosis.
authors: Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou; Department of Gastroenterology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang.
authors: Piaopiao
authors: P
authors: Jin
authors: Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong.
authors: Chi Chun
authors: CC
authors: Wong
authors: Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou.
authors: Sibin
authors: S
authors: Mei
authors: Institute of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
authors: Xingkang
authors: X
authors: He
authors: Institute of Gastroenterology, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
authors: Yun
authors: Y
authors: Qian
authors: Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou.
authors: Leimin
authors: L
authors: Sun
keywords: Akt pathway; MK-2206; apoptosis; caspase; chemotherapy; gastric cancer