title: Cisplatin resistance in gastric cancer cells is associated with HER2 upregulation-induced epithelial-mesenchymal transition.
abstract: Cisplatin remains to be primary chemotherapeutic drug for gastric cancer patients, especially for advanced stage ones. However, primary or acquired resistance often occurs with the mechanisms being not well understood, which results in relapse of the cancer and poor survival. Herein, we found that HER2 upregulation was associated with cisplatin resistance. We observed that cisplatin-resistant gastric cancer cells underwent a morphological change similar to epithelial-mesenchymal transition (EMT) which is mediated by HER2 overexpression. When specific monoclonal antibody Herceptin, small molecular targeted drug CP724714, or small interfering RNA against HER2 was applied, the EMT-like phenotypic change was dramatically reversed. More importantly, the IC50 and Resistance Index of resistant gastric cancer cells to cisplatin were also decreased by any of these treatments.We demonstrated that expression and amplification of HER2 positively correlated with expression of EMT-related transcription factor Snail in gastric cancer tissues. Furthermore, for the first time, we found that HER2/Snail double positive gastric cancer patients had poorer survival than single positive or double negative counterparts, which provided experimental evidence for the necessity of HER2/Snail double testing in gastric cancer. In conclusion, this study provides some clues of the association of cisplatin resistance with HER2 upregulation-induced EMT in gastric cancer cells.
authors: Clinical Research Institute, Zhejiang Provincial People's Hospital, 158 Shangtang Road, Hangzhou 310014, China.
authors: Dongsheng
authors: D
authors: Huang
authors: Clinical Research Institute, Zhejiang Provincial People's Hospital, 158 Shangtang Road, Hangzhou 310014, China.|Department of Pathology, Zhejiang Provincial People's Hospital, 158 Shangtang Road, Hangzhou 310014, China.
authors: Hongying
authors: H
authors: Duan
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital &Institute, Beijing 100142, China.
authors: Hao
authors: H
authors: Huang
authors: Clinical Research Institute, Zhejiang Provincial People's Hospital, 158 Shangtang Road, Hangzhou 310014, China.
authors: Xiangmin
authors: X
authors: Tong
authors: Department of Pathology, Zhejiang Provincial People's Hospital, 158 Shangtang Road, Hangzhou 310014, China.
authors: Yong
authors: Y
authors: Han
authors: Department of Pathology, Zhejiang Provincial People's Hospital, 158 Shangtang Road, Hangzhou 310014, China.
authors: Guoqing
authors: G
authors: Ru
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital &Institute, Beijing 100142, China.
authors: Like
authors: L
authors: Qu
authors: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital &Institute, Beijing 100142, China.
authors: Chengchao
authors: C
authors: Shou
authors: Department of Pathology, Zhejiang Provincial People's Hospital, 158 Shangtang Road, Hangzhou 310014, China.
authors: Zhongsheng
authors: Z
authors: Zhao
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011799:Quinazolines / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016019:Survival Analysis; D015854:Up-Regulation
chemical_list: D002945:Cisplatin; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000071250:Snail Family Transcription Factors; C521104:2-methoxy-N-(3-(4-((3-methyl-4-((6-methyl-3-pyridinyl)oxy)phenyl)amino)-6-quinazolinyl)-2-propenyl)acetamide; C508053:ERBB2 protein, human