血管生成抑制剂抗胃癌微淋巴管生成的实验研究

Study on inhibition of lymphangiogenesis in gastric cancer by NM-3

目的 通过建立未分化人胃腺癌SGC-7901原位移植裸鼠模型,应用2-（8-羟基-6-甲氧基-1-氧-1-氢-2-苯并吡喃-3-羟基）丙酸（NM-3）和卡铂的腹腔化学治疗,观察其对裸鼠原位移植人胃癌微淋巴管生成的影响.方法 建立人胃癌SGC-7901原位种植BALB/C裸鼠模型28只,随机分为4组,每组7只,分别腹腔内注射0.9%氯化钠溶液、NM-3（10 mg/kg）、卡铂（5 mg/kg）和NM-3＋卡铂,2次/周.8周后处死裸鼠,采用定量免疫组化染色检测淋巴管内皮细胞透明质酸受体（LYVE）-1、肾小球足突细胞膜黏蛋白、同源异型盒转录因子（Prox）-1;计数微淋巴管密度（LMVD）值.结果 卡铂组、NM-3组及NM-3＋卡铂组LYVE-1表达值均较0.9%氯化钠溶液组下降,但差异无统计学意义（P值均＞0.05）;NM-3组及NM-3＋卡铂组肾小球足突细胞黏蛋白、Prox-1值较0.9%氯化钠溶液组及卡铂组均显著下降（P＜0.05）.NM-3组及NM-3＋卡铂组LMVD值分别为4.72±0.50和4.78±0.38,较0.9%氯化钠溶液组及卡铂组均显著下降[7.35±0.55和6.98±0.35,P＜0.05].结论 NM-3能抑制胃癌微淋巴管生成,抑制肿瘤的生长和转移.

Abstract：Objective To evaluate the inhibitory effect of 2-（8-hydroxy-6-methoxy-1-oxo-1-H-2-benzopyran-3-Y1） propionic acid （NM-3） on lymphangiogenesis in gastric cancer using orthotopic implantated tumor models of BALB/C nude mice. Methods A BALB/C nude mouse model of transplanted in situ human gastric cancer was established. Twenty-eight nude mice were divided into four groups with 7 each： control group, NM-3 treated group, carboplatin （10 mg/kg） treated group,and NM-3 combiantion group injected with normal saline, 5 mg/kg of NM-3, 10 mg/kg of carboplatin or 5 mg/kg of NM-3, ＋ 10 mg/kg carboplatin, respectively, twice a week for 8 weeks. At the end of the 8th week, all mice were sacrificed for detection of lymphatic microvessel density （LMVD）,lymphatic vessel endothelial hyaluranic acid receptor 1 （LYVE-1）, podoplanin and Prox-1 byimmunohistochemistry with staining. Results In comparison with control group, the LYVE-1 level in other three groups was decreased with no significant difference （P〉 0.05）. The concentrations of podoplanin and Prox-1 in NM-3 group and combination group decreased significantly than those in control group and carboplatin group （P 〈 0.05）. The number of LMVD in NM-3 group and combination group was 4.72±0.50 and 4.78± 0.38, respectively, which was significantly lower than that in control group （7.35±0.55）and carboplatin group （6.98i0.35, P〈0.05）. Conclusion The NM-3 can inhibit the growth of gastric cancer by interfering lymphangiogenesis of gastric cancer.