Autophagy flux inhibition augments gastric cancer resistance to the anti-human epidermal growth factor receptor 2 antibody trastuzumab

Ye,Hua; Chai,Xuyu; Wang,Xiaoyu; Zheng,Qi; Zheng,Dingcheng; Wu,Feng; Zheng,Cheng; Chen,Ping

doi:10.3892/ol.2018.7891

Autophagy flux inhibition augments gastric cancer resistance to the anti-human epidermal growth factor receptor 2 antibody trastuzumab

Authors:
- Hua Ye
- Xuyu Chai
- Xiaoyu Wang
- Qi Zheng
- Dingcheng Zheng
- Feng Wu
- Cheng Zheng
- Ping Chen
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Affiliations: Department of Gastrointestinal and Hernia, Ningbo No. 2 Hospital, Ningbo, Zhejiang 315010, P.R. China, National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai 201203, P.R. China, Laboratory of Immunology and Virology, Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China
Published online on: January 29, 2018 https://doi.org/10.3892/ol.2018.7891
Pages: 4143-4150
Copyright: © Ye et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The autophagy involved in the occurrence, development and prognosis of human epidermal growth factor receptor 2 (HER2) gene-amplified cancer also controls the resistance of this type of cancer to the monoclonal antibody, trastuzumab (Tzb). In the present study, Tzb resistance was established in HER2‑positive NCI‑N87 cell lines (Tzb‑refractory cells). The cell viability, clonogenic assay, ratios of light chain 3 II/I, sequestosome 1 expression, and the phosphorylation of protein kinase B (Akt) and mechanistic target of rapamycin (mTOR) were investigated in the parental and Tzb‑refractory cells. The viability of parental NCI‑N87 and Tzb‑refractory cells with an autophagy inhibitor or inducer was also examined. The results of the present study indicated that autophagic flux may have an important function in the resistance of HER2-positive human gastric cancer NCI‑N87 cells to Tzb. Tzb resistance in NCI‑N87 cells prevents cell apoptosis via autophagic flux inhibition. Tzb may activate the Akt/mTOR pathway to inhibit autophagic flux in gastric cancer cell lines. Everolimus, an mTOR inhibitor, may inhibit cell viability, indicating that the mTOR pathway may serve a function in HER2‑positive gastric cancer and that the resistance of HER2‑positive gastric cancer to Tzb may, at least partially, be due to activation of the mTOR pathway.

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