人参皂甙Rg3对荷卵巢癌的严重联合免疫缺陷鼠的抗肿瘤血管生成作用的研究

Antiangiogenesis of ginsenoside Rg3 in severe combined immunodeficient mice with human ovarian carcinoma

目的 研究人参皂甙Rg3体内抗卵巢癌血管生成的作用。方法 建立荷卵巢癌的严重联合免疫缺陷 (SCID)鼠腹腔移植瘤模型 ,分为 3组。空白组 :SCID鼠荷瘤后不干预 ;对照组 :荷瘤SCID鼠予磷酸盐缓冲液 (PBS)灌胃 ;实验组 :荷瘤SCID鼠予人参皂甙Rg3和PBS混悬液灌胃。分别采用逆转录聚合酶链反应技术、酶联免疫吸附法、免疫组织化学法检测 3组荷瘤SCID鼠的血管内皮生长因子 (VEGF)mRNA、蛋白及微血管密度 (MVD)。结果 (1)人参皂甙Rg3处理后 ,荷瘤SCID鼠体内无腹水形成 ,腹腔中肿块播散减少。 (2 )实验组肿瘤组织VEGFmRNA表达的相对量为 119± 16 ,显著低于空白组、对照组 (分别为 2 5 4± 4和 2 73± 4 4 ,P均 <0 0 5 )。 (3)实验组血中VEGF蛋白的表达量为(14 6± 0 7)pg/ml,显著低于空白组和对照组 [分别为 (18 5± 2 1)和 (2 0 5± 1 7)pg/ml,P均 <0 0 5 ]。(4)实验组肿瘤组织中MVD为 (43± 7)个 /mm3 ,显著低于空白组和对照组 [分别为 (6 5± 12 )个 /mm3 和(73± 10 )个 /mm3 ,P均 <0 0 5 ]。结论 人参皂甙Rg3通过下调肿瘤VEGFmRNA及蛋白的表达量 。

Objective To investigate the antiangiogenesis of ginsenoside Rg3 in severe combined immunodeficient (SCID)mice with human ovarian carcinoma by detecting vascular endothelial growth factor (VEGF) mRNA, VEGF protein level and microvascular density (MVD) Methods The SCID mice with human ovarian carcinoma SKOV3 cells were treated with Rg3 (300 μg 400 μl -1 mouse -1 ), mice with phosphate buffered solution (PBS) and without Rg3 and PBS were used as control Tumor volume, metastasis, ascites, VEGF mRNA, VEGF protein and MVD were detected The level of VEGF mRNA in tumor tissue was determined by relative quantative reverse transcription polymerase chain reaction VEGF protein level in sera and ascitic fluids were determined by enzyme linked immunosorbent assay MVD was calculated by immunohistochemistry (anti CD34) Results (1) No ascites was formed and the size of metastasis decreased in SKOV3/Rg3 group (2) Expression of VEGF mRNA level in SKOV3/Rg3 group (119±16) was lower significantly than those of the control groups (254±4,273±44, respectively, P <0 05) (3) Serum VEGF level in SKOV3/Rg3 group [(14 6±0 7) pg/ml] was lower significantly than those of SKOV3 group and SKOV3/PBS group [(18 5±2 1) and (20 5±1 7) pg/ml, respectively, P <0 05] (4) MVD in tumor tissues of SKOV3/Rg3 group (43±7) was lower than that of each control group (65±12,73±10, respectively, P <0 05) Conclusion Ginsenoside Rg3 can block angiogenesis and inhibit tumor growth and metastasis by downregulating the expression of VEGF mRNA and protein and reducing microvascular density