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

Autor:	Feng Wu, Xiaoyu Wang, Dingcheng Zheng, Qi Zheng, Cheng Zheng, Ping Chen, Hua Ye, Xuyu Chai
Jazyk:	angličtina
Rok vydání:	2018
Předmět:	0301 basic medicine Cancer Research autophagy 03 medical and health sciences 0302 clinical medicine Sequestosome 1 medicine Viability assay education Protein kinase B Mechanistic target of rapamycin PI3K/AKT/mTOR pathway education.field_of_study biology Chemistry Autophagy human epidermal growth factor receptor 2 Cancer Articles Cell cycle medicine.disease trastuzumab 030104 developmental biology Oncology 030220 oncology & carcinogenesis biology.protein Cancer research mechanistic target of rapamycin
Zdroj:	Oncology Letters
ISSN:	1792-1082 1792-1074
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5767cd6502607b253f561002d06901d6 http://europepmc.org/articles/PMC5835962 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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