摘要
目的:研究健脾解毒方对裸鼠人结肠癌血管新生的作用及机制。方法:建立人结肠癌HT-29细胞裸鼠皮下移植瘤模型,随机分为5组:对照组(0.9%氯化钠溶液组),健脾解毒方低、中、高剂量组(250、500、1 000mg·kg-1·d-1)和化疗药顺铂组(1mg·kg-1·d-1)。给药第21天,处死各组荷瘤鼠,比较各组肿瘤大小。免疫组化法检测各组瘤体的微血管密度(MVD)、COX-2和β-catenin表达;ELISA测定血清中血管内皮生长因子(VEGF)、血管生成素(Ang-2)和碱性成纤维细胞生长因子(bFGF)的表达。结果:健脾解毒方低、中、高剂量组的瘤重抑制率分别为30.14%、38.01%、40.36%。免疫组化结果显示,对照组、健脾解毒方低、中、高剂量组瘤体MVD计数分别为(56.00±2.65)、(43.00±1.58)、(28.67±2.53)和(23.33±2.08),与对照组比较差异显著(P<0.01)。ELISA结果显示,健脾解毒方能够显著下调裸鼠血清中VEGF、Ang-2和bFGF表达(P<0.01)。同时,健脾解毒方能够显著下调瘤体中COX-2和β-catenin蛋白表达,呈剂量依赖效应。结论:健脾解毒方能抑制人结肠癌皮下移植瘤的生长和血管新生,其机制可能通过COX-2-Wnt/β-catenin信号通路下调VEGF表达有关。
Objective： To study effects of Jianpi Jiedu Recipe on angrogenesis in nude mice with human colorectal cancer. Methods： The subcutaneous transplantation tumor models of nude mice with human colorectal cancer HT-29 cells were established, and randomly divided into 5 groups： Control group （0.9% sodium chloride solution group）, Jianpi Jiedu Recipe low-, mid- and high-dose group （250, 500, 1 000mg · kg^-1 ·d^-1）, Cisplatin group （lmg· kg^-1 ·d^-1）. All groups of nude mice were sacrificed at the 21st day of the trentment, the size of tumor was measured. The micro vessel density （MVD）, COX-2 and β-catenin were tested by Immunohistochemistry; the vascular endothelial growth factor （VEGF）, Angiopotetion-2 （Ang-2） and basic fibroblast growth factorl （bFGF） expression in serum were assayed by ELISA. Results： The inhibition rate of tumor weight were respectively 30.14%, 38.01%, 40.36% in the Jianpi Jiedu Recipe low, mid, high-dose groups. The MVD in the control group and the Jianpi Jiedu Recipe low-, mid-, high-dose groups were respectively （56.00±2.65）, （43.00±1.58）, （28.67±2.53） and （23.33±2.08）, which obviously decreased compared with the Control group （P〈0.01）. The ELISA results showed that the VEGF, Ang-2 and bFGF expresssion in the Jianpi Jiedu Recipe low-, mid-, high-dose groups obviously decreased compared with the Control group （P〈0.01）. Meanwhile, Jianpi Jiedu Recipe significantly reduced the level of COX-2 and β-catenin in tumor, in dose-dependent relation. Conclusion： Jianpi Jiedu Recipe could inhibit the growth and angiogenesis of subcutaneous transplantation tumor of numan colorectal cancer, which might have a relationship with blocking the COX-2-Wnt/β-catenin signal pathway and reducing VEGF expression.
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2013年第5期1276-1280,共5页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
国家自然科学基金(No.81202812)
上海市科委项目(No.114119B3100
No.09ZR1428500)
上海市中医药科研基金(No.2011ZJ030)~~
