title: Anti-IGF-1R monoclonal antibody inhibits the carcinogenicity activity of acquired trastuzumab-resistant SKOV3.
abstract: BACKGROUND
  Antibody resistance, not only de novo but also acquired cases, usually exists and is related with lower survival rate and high risk of recurrence. Reversing the resistance often results in better clinical therapeutic effect. Previously, we established a trastuzumab-resistant ovarian cancer cell line, named as SKOV3-T, with lower HER2 and induced higher IGF-1R expression level to keep cell survival.
  
  
  METHODS
  IGF-1R was identified important for SKOV3-T growth. Then, a novel anti-IGF-1R monoclonal antibody, named as LMAb1, was used to inhibit SKOV3-T in cell growth/proliferation, migration, clone formation and in vivo carcinogenicity.
  
  
  RESULTS
  In both in vitro and in vivo assays, LMAb1 showed effective anti-tumor function, especially when being used in combination with trastuzumab, which was beneficial to longer survival time of mice as well as smaller tumor. It was also confirmed preliminarily that the mechanism of antibody might be to inhibit the activation of IGF-1R and downstream MAPK, AKT pathway transduction.
  
  
  CONCLUSIONS
  We achieved satisfactory anti-tumor activity using trastuzumab plus LMAb1 in trastuzumab-resistant ovarian cancer model. In similar cases, not only acquired but also de novo, good curative effect might be achieved using combined antibody therapy strategies.
authors.affiliation: Laboratory of Cellular and Molecular Immunology, Institute of Immunology, Henan University, Kaifeng, 475001, China. 1790735517@qq.com.|Laboratory of Immunology, Institute of Basic Medical Sciences, PO Box 130(3), Taiping Road #27, Beijing, 100850, China. 1790735517@qq.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Gynecology and Obstetrics, PLA General Hospital, Fuxing Road No. 28, Beijing, 100853, China. zhangyan_301@126.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, PO Box 130(3), Taiping Road #27, Beijing, 100850, China. lm62033@aliyun.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Lv
authors.affiliation: Laboratory of Cellular and Molecular Immunology, Institute of Immunology, Henan University, Kaifeng, 475001, China. Fengjiannan1970@qq.com.|Laboratory of Immunology, Institute of Basic Medical Sciences, PO Box 130(3), Taiping Road #27, Beijing, 100850, China. Fengjiannan1970@qq.com.
authors.forename: Jiannan
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Environment and Pharmacy, Tianjin Institute of Health and Environmental Medicine, Beijing, 100850, China. p_h2002@hotmail.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Peng
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, PO Box 130(3), Taiping Road #27, Beijing, 100850, China. youhighness@gmail.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Geng
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, PO Box 130(3), Taiping Road #27, Beijing, 100850, China. linzbiodoc77@163.com.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, PO Box 130(3), Taiping Road #27, Beijing, 100850, China. grace.tingting.zhou@gmail.com.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, PO Box 130(3), Taiping Road #27, Beijing, 100850, China. lychee526@126.com.
authors.forename: Xinying
authors.initials: X
authors.lastname: Li
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, PO Box 130(3), Taiping Road #27, Beijing, 100850, China. shenbf@mx.cei.gov.cn.
authors.forename: Beifen
authors.initials: B
authors.lastname: Shen
authors.affiliation: Laboratory of Cellular and Molecular Immunology, Institute of Immunology, Henan University, Kaifeng, 475001, China. mayf@henu.edu.cn.
authors.forename: Yuanfang
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, PO Box 130(3), Taiping Road #27, Beijing, 100850, China. bioqcx1982@hotmail.com.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Qiao
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000068878:Trastuzumab; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D017526:Receptor, IGF Type 1; D000068878:Trastuzumab