鬼臼苦素单用或联合顺铂对上皮性卵巢癌裸鼠移植瘤的抑制作用

Picropodophyllin alone or combination with cisplatin on ovarian cancer in nude mice tumor inhibited

目的:观察鬼臼苦素单用及其与顺铂联合应用对上皮性卵巢癌裸鼠移植瘤的作用,并对其机制进行评价。方法:建立32只人卵巢癌裸鼠移植瘤模型,裸鼠随机分成4组:溶剂对照组(生理盐水)、DDP(5mg/kg)组、PPP(40mg/kg)组、DDP(5mg/kg)+PPP(40mg/kg)组,每隔3天腹腔给药1次,18天后处死,测量裸鼠实验前后体重及肝肾功能,绘制生长曲线,计算抑瘤率;免疫组化法测定肿瘤内磷酸化胰岛素样生长因子-1受体(pIGF-1R)、微血管密度(MVD)、血管内皮生长因子(VEGF)的标记指数,TUNEL方法检测肿瘤细胞凋亡情况。结果:DDP组、PPP组和PPP+DDP组抑瘤率分别为(26.53±8.42)%,(39.18±10.12)%和(72.17±30.79)%,按金正均法计算q值为1.341;PPP组血清丙氨酸转移酶、尿素氮、肌酐值与对照组比较差异无统计学意义(P>0.05),DDP组裸鼠的血清尿素氮、肌酐值与对照组比较差异有统计学意义(P<0.05),DDP组与DDP+PPP组的血清尿素氮、肌酐值与DDP组比较差异无统计学意义(P>0.05)。PPP组和PPP+DDP组移植瘤内pIGF-1R?MVD、VEGF较对照组均明显降低,DDP组移植瘤内MVD、VEGF较对照组有所降低,差异有统计学意义(P>0.05),但均高于PPP组和PPP+DDP组,且与这两组差异有统计学意义(P<0.05)。PPP组,DDP组及PPP+DDP组的凋亡指数与对照组比较均明显升高,以PPP+DDP组最为显著,PPP组凋亡指数高于DDP组差异有统计学意义(P<0.05)。PPP+DDP组与PPP组调亡指数无明显差异(P>0.05)。结论:鬼臼苦素对裸鼠上皮性卵巢移植癌具有抑制生长作用。鬼臼苦素与顺铂存在协同作用,且对裸鼠肝肾功能没有明显的不良反应。鬼臼苦素可能有抑制肿瘤新生血管生成的作用。

Objective： To observe the effect of picropodophyllin alone or in combination with cisplatin to epithelial ovarian transplantable cancer nude mice and evaluate the mechanism. Methods： The establishmen, t of 32 human ovarian cancer xenografts in nude mice were randomly divided into 4 groups： solvent control group （saline）, DDP （5 mg / kg） group, PPP （40 mg / kg） group, DDP （5 mg / kg） ＋ PPP （40 mg / kg） group, intraperitoneal injection every 1 to 3 days, 18 days after the death, measured before and after nude mouse body weight and liver and kidney function test, growth curve, calculation of inhibition rate ; immunohistochemical method tumor phosphorylation of insulin - like growth factor - 1 receptor （ plGF - 1 R） , microvessel density （MVD） , vascular endothelial growth factor （VEGF） in the labeling index, TUNEL to detect tumor cell apoptosis. Results： DDP group, PPP and PPP ＋ DDP group, the tumor inhibition rate was （26. 53 ± 8.42 ）%, （39. 18 ± 10. 12 ）% and （72. 17 ± 30. 79）%, according to Kim Jong are calculated q value of 1. 341 ; PPP serum alanine aminotransferase, blood urea nitrogen, ereatinine, compared with the control group showed no significant difference （P 〉 0. 05 ）, DDP group of nude mice blood urea nitrogen, creatinine compared with the control group significantly （ P 〈 0. 05 ） , DDP group and the DDP ＋ PPP group serum urea nitrogen, creatinine compared with the DDP group the difference was not statistically significant （ P 〉 0. 05 ） . PPP group and PPP ＋ DDP group, the transplanted tumor plGF - 1 R, MVD, VEGF was significantly lower than the control group, DDP group within the tumor MVD, VEGF than the control group decreased significantly （ P 〉 0. 05 ）, but higher than the PPP group and PPP ＋ DDP group, and with both groups significantly （ P 〈0. 05 ） . PPP group, DDP group and PPP ＋ DDP group and control group, the apoptosis index increased significantly compared to PPP ＋ DDP group the most significant, PPP, the apoptosis index was higher than DDP group difference was significant （ P 〈 0. 05 ） . PPP ＋ DDP group and the PPP group no significant difference in apoptosis index （ P 〉 0.05 ） . Conclusion： Picropodophyllin has have synergies with cisplatin , obvious side effects for nude mice liver and renal function. Picropodophyllin may has the function of inhibiting tumor angiogenesis.