姜黄素增强奥沙利铂对结肠癌裸鼠皮下移植瘤的抑制和诱导凋亡作用

Curcum Enhances Anti-tumor Effect of Oxaliplatin on Colorectal Cancer Cell Xenograft

目的:探讨姜黄素增强奥沙利铂对肠癌HT-29细胞裸鼠移植瘤的诱导凋亡作用及其机制。方法:建立耐药肠癌HT-29细胞的裸鼠皮下移植瘤模型,将荷瘤鼠随机分为Con组(生理盐水)、Oxa组(奥沙利铂7.5mg/kg)、Cur组(姜黄素50mg/kg)和Oxa+Cur组(联合用药,奥沙利铂7.5mg/kg和姜黄素50mg/kg)。腹腔注射给药,每3d1次,共8次。给药后测量肿瘤体积。免疫组织化学法检测肿瘤组织细胞增殖因子(Ki-67)、凋亡抑制因子(XIAP)和核转录因子(NF-κB)的蛋白表达。RT-PCR检测NF-κB和XIAPmRNA的表达。结果:Oxa+Cur组肿瘤体积和质量明显小于其他各组。与Con组相比较,Oxa组、Cur组和Oxa+Cur组的Ki-67蛋白表达显著下降;与Oxa组和Cur组相比较,Oxa+Cur组的Ki-67蛋白表达显著下降。与Con组相比较,Oxa组、Cur组和Oxa+Cur组的NF-κB和XIAP蛋白和mRNA的表达显著下降;与Oxa组和Cur组相比较,Oxa+Cur组的NF-κB和XIAP蛋白和mRNA的表达显著下降。结论:姜黄素可以通过下调Ki-67和NF-κB及XIAP基因表达,增强奥沙利铂对肠癌HT-29细胞移植瘤的抑制细胞增殖和诱导凋亡作用。

Objective To investigate the enhanced effect of oxaliplatin by Curcum on HT-29 cell xenograft on athymic. Methods The models of HT-29 cell xenograft on athymic mouse were established and random- ized to four groups with intraperitoneal （IP） injection of different drugs （group Con 0.9% sodium chloride）, group Oxa （oxaliplatin, 7.5 mg/kg）, group Cur （ Cureum 50 mg/kg）and group Oxa＋Cur （oxaliplatin 7.5 mg/kg and Cur- cure 50 mg/kg in combination）. The drugs were injected once every 3 days, 8 times in all. The mice were sacri- ficed 1 week after the last injection. The tumor volume and tumor weight were measured during the drug thera- py. Immunohistoehemistry （IHC） was performed to detect the expression of NF-KB, XIAP and Ki-67, RT-PCR was performed to detect the expression of NF-KB and XIAPmRNA. Results One week after the last adminis- tration, the mean tumor volume and tumor weight in group Oxa＋Cur were significantly dec the other groups. IHC analysis showed the expression of NF-K B and XIAP were down reased as compared to regulated in Cur and Oxa＋Cur groups as compared to the other two groups. The expression of Ki-67 was also down regulated signifi- cantly in Oxa＋Cur group as compared to the other groups. RT-PCR analysis showed the expression of NF-KB and XIAP mRNA in Con and Oxa＋ Cur groups were down regulated significantly as compared to the other groups. Conclusion Curcum can enhance the anti-tumor effect of oxaliplatin on colorectal cancer xenograft. Downregulation of NF-KB and XIAP is possibly one of the mechanisms.