Matsui Yoko, Inomata Masafumi, Tojigamori Manabu, Sonoda Kazuya, Shiraishi Norio, Kitano Seigo
Department of Surgery I, Oita University Faculty of Medicine, Hasama-machi, Oita 879-5593, Japan.
Int J Oncol. 2005 Sep;27(3):681-5.
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.
对于无法切除的胃癌患者,需要新的治疗方法。本研究的目的是调查抗HER2抗体在体外和体内是否能抑制HER2过表达的人胃癌细胞的生长。本研究使用了四种人胃癌细胞系,NCI-N87、MKN-45P、Kato-III和MKN-1。检测了曲妥珠单抗治疗后体外细胞增殖和裸鼠模型皮下肿瘤生长的抑制情况。通过蛋白质印迹分析研究HER2蛋白的表达。检测了曲妥珠单抗对腹膜播散裸鼠存活率的影响。曲妥珠单抗在体外显著降低了HER2过表达的人胃癌细胞系NCI-N87的增殖活性。在移植了皮下肿瘤的裸鼠模型中,曲妥珠单抗显著抑制了NCI-N87细胞的肿瘤生长,随后HER2表达降低。曲妥珠单抗提高了MKN-45P细胞腹膜播散小鼠的存活率。曲妥珠单抗治疗是HER2过表达胃癌新治疗方法的潜在候选方案。