title: Eradication of growth of HER2-positive ovarian cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate in mouse xenograft model.
abstract: OBJECTIVE
  Ovarian cancer is 1 kind of a highly malignant gynecologic tumor, and current treatments have not achieved satisfactory effects. Human epidermal growth factor receptor 2 (HER2)-targeted therapies including trastuzumab and trastuzumab-DM1 (T-DM1) (antibody-cytotoxic drug conjugates) have been applied to treat HER2-overexpressing breast cancers in clinic. In the present study, we explored whether T-DM1 could effectively treat HER2-positive human ovarian carcinoma in vitro and in vivo.
  
  
  METHODS
  HER2 expressions of 6 ovarian cancer cell lines and 2 breast carcinoma cell lines were validated, and the binding capacity of T-DM1 to HER2-positive ovarian cancer SKOV3 cells were analyzed by flow cytometry. Nude mice bearing intraperitoneal and subcutaneous SKOV3 xenografts were used to investigate the antitumor effect of T-DM1.
  
  
  RESULTS
  High HER2 expressions in SKOV3 cell lines were detected. The binding capacity of T-DM1 to HER2-positive SKOV3 cells was in a similar manner comparing with trastuzumab. In vitro, T-DM1 showed strong growth inhibitory on SKOV3 cells, with IC50 values of 0.15 nmol/L. Nude mice bearing intraperitoneal and subcutaneous SKOV3 xenografts were used to investigate the antitumor effects of T-DM1 in vivo. In subcutaneous xenografts model, T-DM1 (30 mg/kg and 10 mg/kg) indicated significant anticancer effects. It is noteworthy that tumors were completely eradicated in the T-DM1 (30 mg/kg) group, and no regrowth was observed in a long time after the termination of the treatment. In the peritoneal xenograft model, tumor nodules in 3 of 7 mice were hardly observed in the abdominal cavity of mice after intraperitoneal injection of T-DM1 (30 mg/kg). At the same time, tumor nodules from the other 4 mice weighed on the average of only 0.07 g versus 1.77 g in control group.
  
  
  CONCLUSIONS
  Our data showed that T-DM1 possessed promising antitumor effects on HER2-overexpressing ovarian cancer in mouse model, which provided valuable references for the future clinical trials.
authors.affiliation: *State Key Laboratory of Biotherapy, and †Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yu
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Yao
authors.forename: Wenting
authors.initials: W
authors.lastname: Li
authors.forename: Qinhuai
authors.initials: Q
authors.lastname: Lai
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Zhou
authors.forename: Tairan
authors.initials: T
authors.lastname: Kang
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Xie
authors.forename: Yangping
authors.initials: Y
authors.lastname: Wu
authors.forename: Xiangzhen
authors.initials: X
authors.lastname: Chen
authors.forename: Cheng
authors.initials: C
authors.lastname: Yi
authors.forename: Lantu
authors.initials: L
authors.lastname: Gou
authors.forename: Jinliang
authors.initials: J
authors.lastname: Yang
mesh_terms: D000080044:Ado-Trastuzumab Emtansine; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D061986:MCF-7 Cells; D008453:Maytansine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000068878:Trastuzumab; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D008453:Maytansine; D000068878:Trastuzumab; D000080044:Ado-Trastuzumab Emtansine