期刊
ONCOTARGET
卷 6, 期 36, 页码 38912-38925出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.5334
关键词
trastuzumab; tunicamycin; breast cancer
资金
- National Natural Science Foundation of China [81272208]
- Natural Science Foundation of Shandong Province of China [ZR2009CM046]
- Shandong Foundation for Development of Science and Technology [2010G0020210]
- Jinan Innovation Plan for University and Institution [201112002]
Trastuzumab, a humanized monoclonal antibody targeting HER2, has demonstrated clinical benefits for women with HER2-positive breast cancer; however, trastuzumab resistance remains the biggest clinical challenge. In this study, results showed that tunicamycin, an inhibitor of N-glycosylation, synergistically enhanced the antitumor activity of trastuzumab against HER2-overexpressing breast cancer cells through induction of cell cycle arrest and apoptosis. Combined treatment of tunicamycin with trastuzumab dramatically decreased the expression of EGFR family and its down signaling pathway in SKBR3 and MCF-7/HER2 cells. Tunicamycin dose-dependently inhibited tumor growth in both of SKBR3 xenografts and MCF-7/HER2 xenografts. Optimal tunicamycin without inducing ER stress in liver tissue significantly increased the antitumor effect of trastuzumab in MCF-7/HER2 xenografts. Combinations of trastuzumab with N-glycosylation inhibitors tunicamycin may be a promising approach for improving clinical efficacy of trastuzumab.
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