Growth inhibition of human gastric adenocarcinoma cells in vitro by STO-609 is independent of calcium/calmodulin-dependent protein kinase kinase-beta and adenosine monophosphate-activated protein kinase

Zhiming Ma; Dacheng Wen; Xudong Wang; Longfei Yang; Tianzhou Liu; Jingjing Liu; Jiaming Zhu; Xuedong Fang

Growth inhibition of human gastric adenocarcinoma cells in vitro by STO-609 is independent of calcium/calmodulin-dependent protein kinase kinase-beta and adenosine monophosphate-activated protein kinase

Am J Transl Res. 2016 Feb 15;8(2):1164-71. eCollection 2016.

Authors

Zhiming Ma¹, Dacheng Wen¹, Xudong Wang¹, Longfei Yang², Tianzhou Liu¹, Jingjing Liu¹, Jiaming Zhu¹, Xuedong Fang³

Affiliations

¹ Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University Changchun 130041, P. R. China.
² Key Laboratory for Molecular and Chemical Genetics of Critical Human Diseases of Jilin Province, The Second Hospital of Jilin University Changchun, P. R. China.
³ Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin UniversityChangchun 130041, P. R. China; Department of General Surgery, China-Japan Union Hospital of Jilin UniversityChangchun, P. R. China.

PMID: 27158402
PMCID: PMC4846959

Abstract

Adenosine monophosphate (AMP)-activated protein kinase is a recently identified downstream target of calcium/calmodulin-dependent protein kinase kinase-beta, and is involved in the regulation of cell metabolism and cell proliferation. STO-609 is a selective antagonist of calcium/calmodulin-dependent protein kinase kinase-beta. In the present study, we found that STO-609 suppressed AMP-activated protein kinase activity, reduced expression of Akt and ERK, and increased cell apoptosis in SNU-1 and N87 cells but not normal gastric epithelial cells (CCL-241). Interestingly, we found such effects of STO-609 on gastric cancer cells were not affected after the knock-down of CaMKK-β and AMPK. In conclusion, STO-609 is an effective cytotoxic agent for gastric adenocarcinoma in vivo.

Keywords: AMP-activated protein kinase; Adenocarcinoma; apoptosis; calcium/calmodulin-dependent protein kinase kinase-beta; gastric carcinoma; short hairpin RNA.