【摘要】 目的:探讨重组激肽释放酶结合蛋白(KBP)对胃癌淋巴管新生的抑制作用及其可能的分子机制。方法:培养SGC-7901胃癌细胞系,建立胃癌裸鼠异位移植瘤模型,了解KBP对胃癌生长和淋巴管新生的抑制作用。免疫组织化学和Western blot方法检测肿瘤细胞和组织中的血管内皮生长因子C(VEGF-C)表达,明确KBP通过减少肿瘤细胞VEGF-C表达抑制肿瘤淋巴管新生和肿瘤生长。结果:腹腔内注射KBP导致胃癌生长抑制,抑制率为61.4%。KBP处理的肿瘤组织中淋巴管密度显著降低,提示KBP可以抑制肿瘤淋巴管生成和肿瘤生长。免疫组织化学和Western blot检测显示KBP处理的SGC-7901胃癌细胞和组织中VEGF-C的表达显著减少。结论:下调VEGF-C在肿瘤细胞和肿瘤组织中的表达,提示KBP可能通过抑制肿瘤淋巴管新生作用,进而抑制肿瘤淋巴转移的作用。更多还原

【Abstract】 Objective To investigate the inhibitory effect of Kallikrein-binding protein(KBP) on lymphangiogenesis of gastric cancer. Methods Heterotopic tumors were established by subcutaneously injection of SGC-7901 cells in the dorsal area of nude mice. When tumors reached a volume of 50 mm3, the mice were randomized into two groups and received intraperitoneal injection of KBP or phosphate buffered saline(PBS), respectively. Tumor growth was measured by caliper in two dimensions, and tumor lymphangiogenesis was determined with tumor lymphatic vessel density of(LVD) by immunohistology. SGC-7901 cells were treated with KBP for 24 h, vascular endothelial growth factor C(VEGF-C) protein level in tumor cells and tissues were examined by immunohistochemical method and Western blot. Results The mean weight of tumors treated with KBP was signifi cantly lower than that of control group, and an average of 61.4 % suppression of primary tumor growth was observed. The tumor growth curve in test group was markedly lower than that in control group. Lymphatic vessel density in tumor tissues receiving KBP treatment was also markedly reduced. KBP treatment markedly reduced VEGF protein level in vitro and in vivo. Conclusion KBP inhibits growth of gastric cancer by reducing VEGF production and Lymphangiogenesis, and is a promising candidate for anti-lymphangiogenic treatment of gastric cancer.更多还原