姜黄素联合顺铂对宫颈癌裸鼠移植瘤生长及淋巴转移的影响

Effects of curcumin combined with cisplatin on growth and lymphatic metastasis of cervical cancer xeno-grafts in nude mice

目的 探讨姜黄素联合顺铂在裸鼠体内的抗宫颈癌作用及其对淋巴转移的影响。方法建立人宫颈癌Caski细胞裸鼠皮下移植瘤模型，采用随机数字表法分为4组：生理盐水对照组（10ml／kg）、姜黄素组（100mg／kg）、顺铂组（3mg／kg）、联合用药组（姜黄素100mg／kg＋顺铂3mg／kg），计算移植瘤体积、抑瘤率。应用实时荧光定量PCR检测Caski细胞裸鼠移植瘤组织中巨噬细胞移动抑制因子（MIF）mRNA及血管内皮生长因子-C（VEGF—C）mRNA的表达。结果姜黄素组、顺铂组以及联合用药组的抑瘤率分别为40．8％、53．3％和60．O％。治疗15d后，对照组、姜黄素组、顺铂组、联合用药组肿瘤体积分别为（123．44±35．62）、（71．72±28．36）、（65．47±18．32）、（53．44±10．79）mm3，姜黄素组、顺铂组及联合用药组裸鼠肿瘤体积增长相对缓慢，联合用药组能更有效地抑制裸鼠肿瘤体积增长，4组间比较差异有统计学意义（F=16．890，P=0．000）。实时荧光定量PCR检测显示，相对于对照组（1．000），姜黄素组、顺铂组、联合用药组MIFmRNA相对表达量分别是0．322±0．094、0．154±0．006、0．136±0．007，差异有统计学意义（F=220．279，P=0．000），VEGF-CmRNA相对表达量分别是0．312±0．068、0．263±0．072、0．221±0．041，组间比较差异有统计学意义（F=143．250，P=0．000）；并且MIFmRNA与VEGF—CmRNA之间存在正相关（r=0．815，P=0．001）。结论姜黄素联合顺铂能够明显抑制人宫颈癌Carski细胞裸鼠移植瘤的生长，其通过下调MIFmRNA和VEGF—CmRNA的表达，进而抑制宫颈癌淋巴转移可能是其抗肿瘤作用的重要机制之一。

Objective To analyze the effects of curcumin combined with cisplatin on the growth and lymphatic metastasis of cervical cancer xenografts in nude mice. Methods The human cervical carcinoma Caski cells xenotransplanted tumor models were established. Inoculated mice were randomly divided into 4 groups according to random number table： control （normal saline 10 m]./kg） , Cur （curcumin 100 mg/kg） , Cis （ cisplatin 3 mg/kg） and Cur ＋ Cis group （ 100 mg/kg curcumin ＋ 3 mg/kg cisplatin）. The tumor volume and anti-tumor rate were calculated. The mRNA levels of macrophage migration inhibitory factor （MIF） and vascular endothelial growth factor-C （VEGF-C） were analyzed by real-time fluorescent quantitative polymerase chain reaction （PCR）. Results The inhibitory rates of Cur group, Cis group and Cur ＋ Cis group were 40.8%, 53.3% and 60.0%. After 15 days treatment, the tumor volumes of the control group, Cur group, Cis group and Cur.＋ Cis group were （123.44±35.62）, （71.72 ±28.36）, （65.47±18.32）, （53.44 ± 10.79）mm3. The growth rates of tumor volume in Cur group, Cis group and Cur ＋ Cis group were slower, Cur ＋ Cis group could more effectively inhibit tumor volume growth. The difference among the four groups had statistically signi- ficance （ F = 16. 890, P = 0.000）. Real-time fluorescent quantitative PCR detection showed that compared with the control group （ 1. 000）, the MIF mRNA expressions in Cur group, Cis group and Cur ＋ Cis group were 0. 322 ±0. 094, 0. 154± 0. 006 and 0. 136 ± 0. 007, VEGF-C mRNA expressions in the three groups were 0.312 ± 0.068, 0. 263 ± 0. 072 and 0.221 ± 0. 041. The differences among groups had statistically significance （ F = 220. 279, P = 0. 000 ; F = 143. 250, P = 0. 000）. MIF mRNA was positively related with VEGF-C mRNA （ r = 0.815, P = 0. 001 ）. Conclusion Curcumin combined with cisplatin can inhibit the growth of Carski cell xenografts in nude mice. Through the down-regulating expression of MIF mRNA and VEGF-C mRNA, cisplatin and curcumin can inhibit the lymphatic metastasis of cervical cancer, and it may be one of the important mechanisms of its anti-tumor effects.