100763
论文已发表
提 交 论 文
注册即可获取Ebpay生命的最新动态
注 册
IF 收录期刊
- 3.3 Breast Cancer (Dove Med Press)
- 3.4 Clin Epidemiol
- 2.5 Cancer Manag Res
- 2.9 Infect Drug Resist
- 3.5 Clin Interv Aging
- 4.7 Drug Des Dev Ther
- 2.7 Int J Chronic Obstr
- 6.6 Int J Nanomed
- 2.5 Int J Women's Health
- 2.5 Neuropsych Dis Treat
- 2.7 OncoTargets Ther
- 2.0 Patient Prefer Adher
- 2.3 Ther Clin Risk Manag
- 2.5 J Pain Res
- 2.8 Diabet Metab Synd Ob
- 2.8 Psychol Res Behav Ma
- 3.0 Nat Sci Sleep
- 1.8 Pharmgenomics Pers Med
- 2.7 Risk Manag Healthc Policy
- 4.2 J Inflamm Res
- 2.1 Int J Gen Med
- 4.2 J Hepatocell Carcinoma
- 3.7 J Asthma Allergy
- 1.9 Clin Cosmet Investig Dermatol
- 2.7 J Multidiscip Healthc
已发表论文
口服变构的 AKT 抑制剂（MK-2206）对人类 鼻咽癌体外和体内的效果影响
Authors Zhao YY, Tian Y, Zhang J, Xu F, Yang YP, Huang Y, Zhao HY, Zhang JW, Xue C, Lam MH, Yan L, Hu ZH, Dinglin XX, Zhang L
Published Date October 2014 Volume 2014:8 Pages 1827—1837
DOI http://dx.doi.org/10.2147/DDDT.S67961
Received 19 May 2014, Accepted 14 July 2014, Published 10 October 2014
Aim: Protein kinase B (AKT) signaling frequently is deregulated in human cancers and plays an important role in nasopharyngeal carcinoma (NPC). This preclinical study investigated the effect of MK-2206, a potent allosteric AKT inhibitor, on human NPC cells in vitro and in vivo.
Methods: The effect of MK-2206 on the growth and proliferation of CNE-1, CNE-2, HONE-1, and SUNE-1 cells was assessed by Cell Counting Kit 8 and colony formation assay. Flow cytometry was performed to analyze cell cycle and apoptosis. The effects of MK-2206 on the AKT pathway were analyzed by Western blotting. Autophagy induction was evaluated via electron microscopy and Western blot. To test the effects of MK-2206 in vivo, CNE-2 cells were subcutaneously implanted into nude mice. Tumor-bearing mice were treated orally with MK-2206 or placebo. Tumors were harvested for immunohistochemical analysis.
Results: In vitro, MK-2206 inhibited the four NPC cell line growths and reduced the sizes of the colonies in a dose-dependent manner. At 72 and 96 hours, the half maximal inhibitory concentration (IC50) values of MK-2206 in CNE-1, CNE-2, and HONE-1 cell lines were 3–5 µM, whereas in SUNE-1, IC50 was less than 1 µM, and MK-2206 induced cell cycle arrest at the G1 phase. However, our study found no evidence of apoptosis. MK-2206 induced autophagy in NPC cells, as evidenced by electron microscopy and Western blot, and inhibited the growth of tumors that were subcutaneously implanted in mice. Inhibition of downstream phosphorylation through the PRAS40 and S6 pathways seems to be the main mechanism for the MK-2206-induced growth inhibition.
Conclusion: Our preclinical study suggests that MK-2206’s antiproliferative effect may be useful for NPC treatment; however, strategies for reinforcing this effect are needed to maximize clinical benefit.
Keywords: AKT inhibitor, MK-2206, nasopharyngeal carcinoma
Methods: The effect of MK-2206 on the growth and proliferation of CNE-1, CNE-2, HONE-1, and SUNE-1 cells was assessed by Cell Counting Kit 8 and colony formation assay. Flow cytometry was performed to analyze cell cycle and apoptosis. The effects of MK-2206 on the AKT pathway were analyzed by Western blotting. Autophagy induction was evaluated via electron microscopy and Western blot. To test the effects of MK-2206 in vivo, CNE-2 cells were subcutaneously implanted into nude mice. Tumor-bearing mice were treated orally with MK-2206 or placebo. Tumors were harvested for immunohistochemical analysis.
Results: In vitro, MK-2206 inhibited the four NPC cell line growths and reduced the sizes of the colonies in a dose-dependent manner. At 72 and 96 hours, the half maximal inhibitory concentration (IC50) values of MK-2206 in CNE-1, CNE-2, and HONE-1 cell lines were 3–5 µM, whereas in SUNE-1, IC50 was less than 1 µM, and MK-2206 induced cell cycle arrest at the G1 phase. However, our study found no evidence of apoptosis. MK-2206 induced autophagy in NPC cells, as evidenced by electron microscopy and Western blot, and inhibited the growth of tumors that were subcutaneously implanted in mice. Inhibition of downstream phosphorylation through the PRAS40 and S6 pathways seems to be the main mechanism for the MK-2206-induced growth inhibition.
Conclusion: Our preclinical study suggests that MK-2206’s antiproliferative effect may be useful for NPC treatment; however, strategies for reinforcing this effect are needed to maximize clinical benefit.
Keywords: AKT inhibitor, MK-2206, nasopharyngeal carcinoma
Download Article[PDF]
