Suppression of tumor growth in human gastric cancer with HER2 overexpression by an anti-HER2 antibody in a murine model.
New modalities are necessary for the treatment of patients with unresectable gastric cancer. The aim of this study was to investigate whether or not anti-HER2 antibody could suppress the growth of human gastric cancer cells with HER2 overexpression in vitro and in vivo. Four human gastric cancer cell lines, NCI-N87, MKN-45P, Kato-III, and MKN-1, were used in this study. The suppression of cell proliferation in vitro and of subcutaneous tumor growth in a nude mouse model after treatment with trastuzumab was examined. The expression of HER2 protein was investigated by Western blot analysis. The effect of trastuzumab on the survival rate of nude mice with peritoneal dissemination was examined. Trastuzumab significantly reduced proliferative activity in NCI-N87, a HER2-overexpressing human gastric cancer cell line, in vitro. In the nude mouse model with transplanted subcutaneous tumor, trastuzumab significantly suppressed the tumor growth of NCI-N87 cells, and then HER2 expression was reduced. Trastuzumab improved the survival rate of mice with peritoneal dissemination of MKN-45P cells. Trastuzumab therapy is a potential candidate for a novel treatment of HER2-overexpressing gastric cancer.
Matsui
Yoko
Y
Department of Surgery I, Oita University Faculty of Medicine, Hasama-machi, Oita 879-5593, Japan. skyyoko@med.oita-u.ac.jp
Inomata
Masafumi
M
Tojigamori
Manabu
M
Sonoda
Kazuya
K
Shiraishi
Norio
N
Kitano
Seigo
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001201:Ascites / Q000473:pathology / Q000517:prevention & control; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010537:Peritoneum / Q000187:drug effects / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000276:immunology; D013274:Stomach Neoplasms / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D016019:Survival Analysis; D015996:Survival Rate; D013997:Time Factors; D000068878:Trastuzumab; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab