Aoyagi Keishiro, Kouhuji Kikuo, Miyagi Motoshi, Kizaki Junya, Isobe Taro, Hashimoto Kousuke, Shirouzu Kazuo
Keishiro Aoyagi, Kikuo Kouhuji, Motoshi Miyagi, Junya Kizaki, Taro Isobe, Kousuke Hashimoto, Kazuo Shirouzu, Department of Surgery, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
World J Crit Care Med. 2013 Nov 4;2(4):48-55. doi: 10.5492/wjccm.v2.i4.48.
To clarify the significance of vascular endothelial growth factor (VEGF) in peritoneal metastasis from gastric cancer, using the gastric cancer cell line MKN-45 compared with the high potential peritoneal dissemination gastric cancer cell line MKN-45P.
The supernatant of culture medium of MKN-45 cells or MKN-45P cells was collected and the concentrations were measured of various cytokines, matrix metalloproteinases, growth factor and angiogenic factors, including VEGF. We performed an initial pilot study to explore whether bevacizumab, a humanized monoclonal antibody against VEGF, had any suppressive effect on the peritoneal dissemination from gastric cancer in an experimental nude mouse model of peritoneal metastasis.
The concentrations of interleukin-6 (IL-6), IL-8, VEGF and matrix metalloproteinase-2 protein in the culture supernatant were each significantly higher than each of those for MKN-45. In the in vivo study, the volume of ascites and the mitotic index were significantly lower in the therapy group than in the non-therapy group. The survival curve of the therapy group was significantly higher than that of the non-therapy group. These results suggested that VEGF was correlated with peritoneal metastasis from gastric cancer.
Findings suggested that bevacizumab for inhibiting VEGF could suppress peritoneal dissemination from gastric cancer.
通过将胃癌细胞系MKN - 45与具有高腹膜播散潜能的胃癌细胞系MKN - 45P进行比较,阐明血管内皮生长因子(VEGF)在胃癌腹膜转移中的意义。
收集MKN - 45细胞或MKN - 45P细胞的培养基上清液,检测包括VEGF在内的多种细胞因子、基质金属蛋白酶、生长因子和血管生成因子的浓度。我们进行了一项初步的探索性研究,以探讨抗VEGF人源化单克隆抗体贝伐单抗在腹膜转移实验裸鼠模型中对胃癌腹膜播散是否有抑制作用。
培养上清液中白细胞介素 - 6(IL - 6)、IL - 8、VEGF和基质金属蛋白酶 - 2蛋白的浓度均显著高于MKN - 45的相应浓度。在体内研究中,治疗组的腹水量和有丝分裂指数显著低于非治疗组。治疗组的生存曲线显著高于非治疗组。这些结果表明VEGF与胃癌腹膜转移相关。
研究结果表明,抑制VEGF的贝伐单抗可抑制胃癌的腹膜播散。