青蒿琥酯对人乳腺癌MCF-7血管生成和肿瘤浸润作用研究  

The effect of artesunate on angiogenesis and tumor infiltration in human breast carcinoma MCF-7

作　　者：董海鹰[1] 王知非[2] 

机构地区：[1]浙江省人民医院泌尿外科肿瘤中心 [2]浙江省人民医院肝胆胰及微创外科

出　　处：《中国临床药理学与治疗学》2015年第5期537-540,524,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：黑龙江省青年科学技术专项资金项目(QC05C46);黑龙江省卫生厅资助(2005-47);2014年浙江省中医药科学研究基金项目(2014ZB004);2015年浙江省自然科学基金面上项目(LY15H160055);2015浙江省卫计委面上项目(201312171)

摘　　要：目的:观察青蒿琥酯对人乳腺癌MCF-7血管生成及浸润转移的抑制作用。方法:建立人乳腺癌MCF-7裸鼠移植瘤模型,给予不同剂量青蒿琥酯治疗并观察其对移植瘤的抑制作用;用免疫组化检测移植瘤组织细胞中VEGF、HIF-1α、u PA、E-cadherin蛋白表达和Western blot检测移植瘤组织细胞中HIF-1α、VEGF蛋白表达。结果:青蒿琥酯低、高剂量组抑瘤率分别为(24.39±10.20)%、(40.24±7.02)%;免疫组化结果显示,与生理盐水组比较,青蒿琥酯低、高剂量组VEGF、HIF-1α蛋白表达显著降低,差异具有统计学意义(P<0.05);u PA和E-cadherin蛋白在生理盐水组和青蒿琥酯低、高剂量组中的表达水平差异均无统计学意义(P>0.05),HIF-1α/VEGF之间表达呈正相关(r=0.983,P=0.000);Western blot结果显示,青蒿琥酯低、高剂量组中VEGF、HIF-1α蛋白下调,表达量低于生理盐水组,青蒿琥酯高剂量组的蛋白表达量最低。HIFlα与VEGF蛋白表达之间存在一致性。结论:青蒿琥酯可显著抑制乳腺癌裸鼠移植瘤的生长,其机制可能与抗肿瘤血管及抑制肿瘤侵袭相关。AIM： AIM： To explore the effect of artesunate on the angiogenesis and tumor infiltration in human breast carcinoma MCF-7. METHODS：The human breast tumor cell line MCF-7 was transplanted into nude mice,and the animals were treated with various doses of ART and normal saline（NS） was as control. The tumor inhibitory effects were measured and compared. The expression of angiogenesis-related proteins VEGF and HIF-1α were detected by immunohistochemistry and western blot.Urokinase plasminogen activator（ u PA） and E-cadherin expressions were detected by immunohistochemistry. RESULTS： The tumor inhibition rates in the low dose ART group,high dose ART group were（ 24. 39 ± 10. 20） % and（ 40. 24 ± 7. 02）%, respectively. Immunohistochemical results showed that compared with the normal saline group,the expressions of VEGF and HIF-α were significantly reduced,there were statistically significant difference（ P〈0. 05）. And the expression levels of u PA and E-cadherin between the treatment groups and the normal saline group were statistically insignificant（ P〈0. 05）. The expression of HIF-lα and VEGF were positively correlated（ r = 0. 983,P =0. 000）. Western blot results showed that compared with the normal saline group, the expressions of VEGF and HIF-1α were significantly reduced.CONCLUSION： Artesunate inhibits the growth of MCF-7 xenograft mouse,its mechanism is related to inhibiting angiogenesis and tumor infiltration.

关 键 词：青蒿琥酯 裸鼠 乳腺癌 血管生成 浸润 

分 类 号：R965.2[医药卫生—药理学]