Aclidinium bromide inhibits the growth and metastasis of gastric cancer MKN‑28 cells via the PI3K signaling pathway

Yuanzhi Wang, Ping Cui, Jingjing Liu, Hongxia Wu, Jun Ma
2018 Molecular Medicine Reports  
The present study investigated the effect and underling mechanisms of aclidinium bromide, a novel, inhaled long-acting muscarinic antagonist, on the development of gastric cancer. Human gastric cancer MKN-28 cells, as a model in vitro, were treated with aclidinium bromide and dimethyl sulfoxide. Cell Counting Kit-8 assay, transwell assay and flow cytometry were used to assess cell proliferation, invasion/migration and apoptosis, respectively. In addition, western blotting was performed to
more » ... performed to determine the relative expression of proteins associated with apoptosis and the phosphatidylinositol-3-kinase (PI3K) signaling pathway. Optical density values of MKN-28 cells were decreased in a time-and dose-dependent manner in the aclidinium bromide treated group. Matrigel invasion analysis demonstrated the number of invasive cells were significantly decreased in the aclidinium bromide-treated group when compared with the control group. Furthermore, aclidinium bromide led to the marked reduction of the number of MKN-28 cells passing though the microwells of the transwell chamber. The expression levels of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) decreased, and the expression of pro-apoptotic proteins active Caspase3 and Bcl-2-associated X protein increased concurrently following aclidinium bromide stimulation using western blotting. The phosphorylation of protein kinase B and mechanistic target of rapamycin were significantly inhibited in MKN-28 cells treated with aclidinium bromide; and the activity of the downstream proteins such as p70S6K and Cyclin D1 were also significantly decreased. In conclusion, aclidinium bromide could inhibit gastric cancer cell proliferation and metastasis, which may be associated with the enhancement of apoptosis induced by the PI3K signaling pathway.
doi:10.3892/mmr.2018.9220 pmid:29956761 fatcat:2lwokeww7vep7kapshir5vn5ta