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

Wang,Yuanzhi; Cui,Ping; Liu,Jingjing; Wu,Hongxia; Ma,Jun

doi:10.3892/mmr.2018.9220

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

Authors:
- Yuanzhi Wang
- Ping Cui
- Jingjing Liu
- Hongxia Wu
- Jun Ma
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Affiliations: Department of Operating, Binzhou Central Hospital, Binzhou, Shandong 251700, P.R. China, Department of Oncology, Binzhou City TB Prevention and Control of Hospital, Binzhou, Shandong 251700, P.R. China, Department of Neurosurgery, Binzhou Central Hospital, Binzhou, Shandong 251700, P.R. China, Department of Nursing, Binzhou Central Hospital, Binzhou, Shandong 251700, P.R. China, Department of Infectious Diseases, Binzhou City TB Prevention and Control of Hospital, Binzhou, Shandong 251700, P.R. China
Published online on: June 25, 2018 https://doi.org/10.3892/mmr.2018.9220
Pages: 2263-2268

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Abstract

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 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.

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