Anti-IGF-1R monoclonal antibody inhibits the carcinogenicity activity of acquired trastuzumab-resistant SKOV3

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• 作者：Wei Wang (1) (2)
  Yan Zhang (3)
  Ming Lv (2)
  Jiannan Feng (1) (2)
  Hui Peng (4)
  Jing Geng (2)
  Zhou Lin (2)
  Tingting Zhou (2)
  Xinying Li (2)
  Beifen Shen (2)
  Yuanfang Ma (1)
  Chunxia Qiao (2)
  
  1. Laboratory of Cellular and Molecular Immunology ; Institute of Immunology ; Henan University ; Kaifeng ; 475001 ; China
  2. Laboratory of Immunology ; Institute of Basic Medical Sciences ; PO Box 130(3) ; Taiping Road #27 ; Beijing ; 100850 ; China
  3. Department of Gynecology and Obstetrics ; PLA General Hospital ; Fuxing Road No. 28 ; Beijing ; 100853 ; China
  4. Department of Environment and Pharmacy ; Tianjin Institute of Health and Environmental Medicine ; Beijing ; 100850 ; China
  
• 关键词：IGF ; 1R ; Monoclonal antibody ; Acquired resistant ; Trastuzumab ; Ovarian cancer
• 刊名：Journal of Ovarian Research
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：7
• 期：1
• 全文大小：1,929 KB
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• 刊物主题：Gynecology; Reproductive Medicine;
• 出版者：BioMed Central
• ISSN：1757-2215

文摘

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. Conclusion 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.