title: Relevance of E-cadherin expression to EGFR-TKI molecular targeted therapy sensitivity/resistance and its clinical significance.
abstract: We examined the effect of E-cadherin expression on epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) molecular targeted therapy sensitivity/resistance. We treated MCF-7, MDA-MB-231, T24, SiHa, H460, SK-HEP-1, MHCC97-H, and THP-1 cells with the EGFR-TKIs PD153035 and gefitinib, and then tested the drug-resistance and sensitivity using the MTT method, calculated IC50 values for each cell line, and compared the results to E-cadherin content. The MTT assay was used to determine the survival rates of MCF-7, MDA-MB-231, T24, SiHa, H460, SK-HEP-1, MHCC97-H, and THP-1 cells upon the action of EGFR-TKI (PD153035, gefitinib). For PD153035, the IC50 in MCF-7, MDA-MB-231, T24, and SiHa cells differed from that of H460, SK-HEP-1, MHCC97-H, and THP-1 (P < 0.05). Following gefitinib treatment, the IC50 values of MCF-7, MDA-MB-231, T24, and SiHa cells differed from those of H460, SK-HEP-1, MHCC97-H, and THP-1 cells (P < 0.01). The survival rate of MCF-7, MDA-MB-231, T24, and SiHa cells clearly decreased with increasing drug concentration, indicating the cells were sensitive to the drugs and that E-cadherin expression was positive; however, H460, SK-HEP-1, MHCC97-H, and THP-1 cells showed no significant decreased with increasing drug concentration, indicating that they were resistant to the drugs and that E-cadherin expression was negative. The survival rate of epithelial tumor cells through the action of EGFR-TKI is related to E-cadherin expression. E-cadherin may play a significant role in the sensitivity regulation of EGFR molecular targeting treatment. E-cadherin may provide important clues for selecting proper EGFR-TKI molecular targeting treatment.
authors.affiliation: Institute of Hepatopancreatobiliary Surgery,China Three Gorges University, Yichang, Hubei, China.
authors.forename: R C
authors.initials: RC
authors.lastname: Xing
authors.affiliation: Institute of Hepatopancreatobiliary Surgery,China Three Gorges University, Yichang, Hubei, China zhengjun1995@163.com.
authors.forename: J
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Pharmacology, Medical Science College, China Three Gorges University, Yichang Hubei, China.
authors.forename: W H
authors.initials: WH
authors.lastname: Zheng
authors.affiliation: Department of Cardiothoracic Surgery, People's Hospital of China Three Gorges University, Yichang, Hubei, China.
authors.forename: Z P
authors.initials: ZP
authors.lastname: Qin
authors.affiliation: Institute of Hepatopancreatobiliary Surgery,China Three Gorges University, Yichang, Hubei, China.
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.affiliation: Institute of Hepatopancreatobiliary Surgery,China Three Gorges University, Yichang, Hubei, China.
authors.forename: R C
authors.initials: RC
authors.lastname: Yao
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000077156:Gefitinib; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D015820:Cadherins; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib; C088860:4-((3-bromophenyl)amino)-6,7-dimethoxyquinazoline