右旋柠烯乳剂对人胃癌移植瘤生长和转移的抑制作用

目的　研究并探讨右旋柠烯乳剂 (D limonene)对人胃癌生长和转移的抑制作用及其机制。　方法　采用人胃癌BGC 82 3细胞株经反复传代成实体瘤的完整组织块 ,建立人胃癌裸小鼠原位移植瘤模型。将 4 0只荷瘤裸小鼠随机分成 4组 ,移植后第 5d开始分别用生理盐水灌胃、5 氟尿嘧啶 (5 FU)腹腔注射、D limonene灌胃、D limonene灌胃 +5 FU腹腔注射共 7周。第 8周处死动物 ,测量原位肿瘤瘤重并计算抑瘤率 ,检测肿瘤细胞凋亡指数 (AI)、肿瘤微血管密度 (MVD)及免疫组织化学测定肿瘤组织血管内皮生长因子 (VEGF)的表达变化 ,光镜与电镜观察组织细胞超微结构变化 ;观察荷瘤鼠腹膜、肝、其他脏器肿瘤转移及腹水情况。　结果　D limonene组、联用组分别与对照组相比 ,胃癌的原位肿瘤瘤重与抑瘤率、AI、MVD、VEGF下调 ,差异有显著性 (P <0 0 5 )。腹膜、肝转移受到明显抑制 (P <0 0 5 )。　结论　D limonene通过抑制肿瘤微血管形成 ,诱导胃癌细胞凋亡 ,抑制了体内胃癌的生长和转移。

INHIBITION OF GROWTH AND METASTASIS OF HUMAN GASTRIC CANCER IMPLANTED IN NUDE MICE BY D-LIMONENE

Objective To study the effects and mechanism of D-limonene on the growth and metastasis of gastric cancer in vivo. Methods Metastatic model simulating human gastric cancer was established by orthotopic implantation of histologically intact human tumor tissue into gastric wall of nude mice.D-limonene was orally administered at dose of 15ml/kg every other day for seven weeks. Eight weeks after implantation, tumor weight, MVD, apoptotic index(AI), electron microscopy was used to observe the super structure changes of tumor;variation of ultra-structure, and the presence of metastasis were evaluated respectively after the mice were sacrificed. Results The growth and metastasis of human gastric cancer implanted in nude mice were significantly inhibited in D-limonene group and combined group than that in control group by tumors in weight, MVD and VEGF, the AI and inhibition rate were increased significantly(P<0.05). The incidences of peritoneal metastasis and liver metastasis also decreased significantly in D-limonene group and combined group than that in control group, 5-FU group(P<0.05).Conclusion D-limonene can induce apoptosis in gastric cancer by inhibiting tumor angiogenesis and has strong inhibitory effect both on tumor growth and metastasis of human gastric cancer implanted in nude mice.