姜黄素对人宫颈癌Caski细胞裸鼠移植瘤MIF和VEGF-C表达的影响

Effects of Curcumin on the Expressions of MIF and VEGF-C in the Human Cervical Cancer Caski Cells Xenografts in Nude Mice

目的探讨姜黄素对人宫颈癌Caski细胞裸鼠移植瘤巨噬细胞移动抑制因子(MIF)、血管内皮生长因子(VEGF)VEGF-C表达的影响,以探讨其抗肿瘤机制。方法建立裸鼠人宫颈癌Caski细胞移植瘤动物模型,成瘤后动物模型随机分为5组,每组7只:阴性对照组、顺铂组(3 mg·kg-1·d-1)和3个姜黄素组(50 mg·kg-1·d-1、100 mg·kg-1·d-1、200 mg·kg-1·d-1)。实验结束后处死各组裸鼠,剥取瘤体并称重,同时寻找淋巴转移灶。应用RT-PCR和免疫组化法检测瘤组织中MIF、VEGF-C mRNA及蛋白的表达。结果 1)RT-PCR结果显示3个姜黄素组(50 mg·kg-1·d-1、100 mg·kg-1·d-1、200 mg·kg-1·d-1)及顺铂组瘤组织中MIF、VEGF-C mRNA的相对表达量较阴性对照组显著减少(P<0.05);MIF mRNA在姜黄素50 mg·kg-1·d-1组的表达与姜黄素100 mg·kg-1·d-1组、姜黄素200 mg·kg-1·d-1组的表达比较差异无统计学意义(P>0.05),与顺铂组表达比较差异有统计学意义(P<0.05);VEGF-C mRNA在姜黄素50mg·kg-1·d-1组的表达与姜黄素100 mg·kg-1·d-1组、姜黄素200 mg·kg-1·d-1组及顺铂组表达比较差异有统计学意义(P<0.05);2)免疫组化统计结果显示:3个姜黄素组(50 mg·kg-1·d-1、100mg·kg-1·d-1、200 mg·kg-1·d-1)及顺铂组瘤组织中VEGF-C、MIF蛋白表达明显低于阴性对照组,差异有统计学意义(P<0.05)。结论姜黄素可能是通过降低人宫颈癌Caski细胞裸鼠移植瘤中MIF、VEGF-C的表达发挥抗宫颈癌淋巴转移作用。

Objective To investigate the effects of curcumin on the expressions of macrophage migration inhibitory factor（ MIF） and vascular endothelial growth factor（ VEGF）-C in the human cervical cancer Caski cells xenografts in nude mice for clarifying their possible mechanism of anti tumor. Methods Nude mice were randomized into the negative control group,the cisplatin group（ 3 mg · kg- 1· d- 1） and the three curcumin groups（ 50mg·kg^- 1·d^- 100 mg·kg^- 1·d^- 100 mg·kg^- 1·d^- 1after establishing the human cervical cancer Caski cells xenografts. RT-PCR and immunohistochemistry were used to detect the mRNA and protein expressions of MIF and VEGF-C in the tumor tissues. Results 1） The mRNA levels of MIF and VEGF-C in the tumor tissue of the cisplatin group and the three curcumin groups（ 50 mg·kg^- 1·d^- 100 mg·kg^- 1·d^- 100 mg·kg^- 1·d^- 1ere significantly lower than those of the negative control group（ P 〈0. 05）; there were no statistical differences in the mRNA level of MIF in the tumor tissue between the 50 mg · kg- 1· d- 1curcumin group and the 100mg·kg^- 1·d^- 1rcumin group or the 200 mg · kg- 1·d- 1curcumin group（ P 〈0. 05）; there was statistical difference in the mRNA level of MIF in the tumor tissue between the 50 mg·kg^- 1·d^- 1rcumin group and the cisplatin group（ P 〈0. 05）; there were statistical differences in the mRNA level of VEGF-C in the tumor tissue between the 50 mg·kg^- 1·d^- 1rcumin group and the 100 mg · kg- 1· d- 1curcumin group or the 200mg·kg^- 1·d^- 1rcumin group or the cisplatin group（ P 〈0. 05）; 2） The protein levels of MIF and VEGF-C in the tumor tissue of the cisplatin group and the three curcumin groups（ 50 mg·kg^- 1·d^- 100 mg·kg^- 1·d^- 100 mg·kg^- 1·d^- 1were significantly lower than those of the negative control group（ P 〈0. 05）. Conclusion Curcumin can prevent the lymphatic metastasis of cervical cancer by reducing MIF,VEGF-C expression of human cervical cancer Caski cells xenografts in nude mice.