PMID- 22458639 OWN - NLM STAT- MEDLINE DCOM- 20140402 LR - 20181202 IS - 1442-2050 (Electronic) IS - 1120-8694 (Linking) VI - 26 IP - 5 DP - 2013 Jul TI - Lapatinib, a dual inhibitor of epidermal growth factor receptor and human epidermal growth factor receptor 2, potentiates the antitumor effects of cisplatin on esophageal carcinoma. PG - 487-95 LID - 10.1111/j.1442-2050.2012.01332.x [doi] AB - Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) overexpression occurs in over 30% of esophageal carcinomas. Combination therapies of EGFR- and HER2-targeting agents with cytotoxic agents are considered a potential therapeutic strategy for esophageal cancer. The antitumor effects of lapatinib, a dual tyrosine kinase inhibitor of EGFR and HER2, cisplatin alone, and the combination of the two drugs on esophageal cancer cells were evaluated. The growth inhibition activity of lapatinib, cisplatin, and lapatinib plus cisplatin was measured by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assays, and the combination index values were calculated. Additionally, cell cycle distribution and cell apoptosis treated with lapatinib or cisplatin alone and the combination of the two drugs were detected by flow cytometry analysis. The activation of EGFR and HER2 signaling pathways was monitored by Western blot analysis. These experimental data showed that the combination of lapatinib and cisplatin synergistically inhibited cell proliferation and exhibited an enhanced pro-apoptotic effect on esophageal cancer cells. The underlying mechanisms of potentiated effects of combined treatment were associated with reduced phosphorylation of EGFR and HER2, and the downstream signaling molecules AKT and extracellular regulated protein kinases (ERK). Our findings indicated that the combination of lapatinib and cisplatin is one of the promising treatment strategies for esophageal carcinomas with EGFR and HER2 overexpression. CI - (c) 2012 Copyright the Authors. Journal compilation (c) 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus. FAU - Guo, X F AU - Guo XF AD - Xinxiang Medical University, Xinxiang The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan Province, China. guoxiaofang_1981@126.com FAU - Zhu, X F AU - Zhu XF FAU - Zhong, G S AU - Zhong GS FAU - Deng, B G AU - Deng BG LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Retracted Publication DEP - 20120327 PL - United States TA - Dis Esophagus JT - Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus JID - 8809160 RN - 0 (Antineoplastic Agents) RN - 0 (Quinazolines) RN - 0VUA21238F (Lapatinib) RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - Q20Q21Q62J (Cisplatin) SB - IM RIN - Dis Esophagus. 2014 Nov-Dec;27(8):802. PMID: 25513704 MH - Antineoplastic Agents/*therapeutic use MH - Apoptosis/drug effects MH - Carcinoma/*drug therapy/metabolism MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Cisplatin/*therapeutic use MH - Drug Synergism MH - ErbB Receptors/antagonists & inhibitors/metabolism MH - Esophageal Neoplasms/*drug therapy/metabolism MH - G2 Phase Cell Cycle Checkpoints/drug effects MH - Humans MH - Lapatinib MH - M Phase Cell Cycle Checkpoints/drug effects MH - Quinazolines/pharmacology/*therapeutic use MH - Receptor, ErbB-2/antagonists & inhibitors/metabolism MH - Signal Transduction/drug effects OTO - NOTNLM OT - EGFR OT - HER2 OT - cisplatin OT - esophageal cancer OT - lapatinib EDAT- 2012/03/31 06:00 MHDA- 2014/04/03 06:00 CRDT- 2012/03/31 06:00 PHST- 2012/03/31 06:00 [entrez] PHST- 2012/03/31 06:00 [pubmed] PHST- 2014/04/03 06:00 [medline] AID - 10.1111/j.1442-2050.2012.01332.x [doi] PST - ppublish SO - Dis Esophagus. 2013 Jul;26(5):487-95. doi: 10.1111/j.1442-2050.2012.01332.x. Epub 2012 Mar 27.