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Tumor Biology
Published in: Tumor Biology 7/2016

01-07-2016 | Original Article

Silencing A7-nAChR levels increases the sensitivity of gastric cancer cells to ixabepilone treatment

Authors: Chao-Chiang Tu, Chien-Yu Huang, Wan-Li Cheng, Chin-Sheng Hung, Yu-Jia Chang, Po-Li Wei

Published in: Tumor Biology | Issue 7/2016

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Abstract

Gastric cancer is an important health issue worldwide. Currently, improving the therapeutic efficacy of chemotherapy drugs is an important goal of cancer research. Alpha-7 nicotine acetylcholine receptor (A7-nAChR) is the key molecule that mediates gastric cancer progression, metastasis, and therapy responses; however, the role of A7-nAChR in the therapeutic efficacy of ixabepilone remains unclear. A7-nAChR expression was silenced by small interfering RNA (siRNA) technology. The cytotoxicity of ixabepilone was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and ixabepilone-induced apoptosis was analyzed by flow cytometry and annexin V/propidium iodide (PI) apoptotic assay. The expression patterns of anti-apoptotic proteins (AKT, phospho-AKT, Mcl-1, and Bcl-2) and pro-apoptotic proteins (Bad and Bax) were determined by western blot. Our study found that A7-nAChR knockdown (A7-nAChR-KD) AGS cells were more sensitive to ixabepilone administration than scrambled control AGS cells. We found that A7-nAChR knockdown enhanced ixabepilone-induced cell death as evidenced by the increased number of annexin V-positive (apoptotic) cells. After scrambled control and A7-nAChR-KD cells were treated with ixabepilone, we found that pAKT and AKT levels were significantly reduced in both groups of cells. The levels of Bcl-2 and the anti-apoptotic Mcl-1 isoform increased dramatically after ixabepilone treatment in scrambled control cells but not in A7-nAChR-KD cells. Bad and Bax levels did not change between the treatment group and vehicle group in both A7-nAChR-KD and scrambled control cells, whereas cleaved PARP levels dramatically increased in ixabepilone-treated A7-nAChR-KD cells. Our results demonstrated that knockdown of A7-nAChR enhanced the sensitivity of gastric cancer cells to ixabepilone administration. Thus, the A7-nAChR expression level in patients with gastric cancer may be a good indicator of ixabepilone sensitivity.
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Metadata
Title
Silencing A7-nAChR levels increases the sensitivity of gastric cancer cells to ixabepilone treatment
Authors
Chao-Chiang Tu
Chien-Yu Huang
Wan-Li Cheng
Chin-Sheng Hung
Yu-Jia Chang
Po-Li Wei
Publication date
01-07-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 7/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4751-x

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