汉防己甲素抑制血管生成的作用

背景与目的:血管生成在肿瘤从良性向恶性转变、癌细胞进入血液循环、转移灶发展和破裂中都起着重要作用.本研究探讨汉防己甲素对体外、体内血管生成的抑制作用及其可能的机制.方法:采用M1_r法观察汉防己甲素对人脐静脉血管内皮细胞(human umbilical vein endothelial cell HUVEC)和人肠癌LoVo细胞增殖的影响.通过Transwell小室趋化实验、体外小管形成实验观察汉防己甲素对HUVEC迁移、成血管能力的影响.建立裸鼠kIVo细胞皮下移植瘤模型.给予汉防己甲素灌胃,观察用药对肿瘤微血管密度的影响.结果:2-8 μg/mL的汉防己甲素作用48 h时对HUVEC的细胞增殖抑制率为24.6%-76.9%,对LoVo细胞增殖抑制率为11.6%～14.0%;体外小管形成实验发现.2～8 μg/mL的汉防己甲素作用24 h时HUVEC小管形成数目减少,且管腔不完整,与对照组比较差异有统计学意义(P值均＜0.001).经2-8 μg/mL的汉防己甲素处理12 h后HUVEC迁移数明显少于对照组(P值均＜O.001).在裸鼠皮下移植瘤体内实验中,80 mg/kg汉防己甲素作用于裸鼠LoVo细胞皮下移植瘤后其微血管密度与生理盐水对照组比较.差异具有统计学意义(p0.035).结论:汉防己甲素在体外能有效抑制血管生成,其机制可能与抑制HUVEC增生、迁移和小管形成,诱导HUVEC凋亡,抑制HUVEC DNA的合成有关.汉防己甲素在体内对裸鼠LoVo移植瘤具有抗血管生成作用.

Inhibitory effect of tetrandrine on angiogenesis

BACKGROUND & OBJECTIVES: Angiogenesis plays an important role in tumorigenesis and metastasis. This study was to investigate the inhibitory effect and mechanism of tetrandrine on angiogenesis in vitro and in vivo. METHODS: MTT assay was used to observe the effect of tetrandrine on the proliferation of human umbilical vein endothelial cells (HUVECs) and human colorectal carcinoma LoVo cells. Transwell migration assay and tube formation assay were used to observe the impact of tetrandrine on cell migration and tube forming ability of HUVECs. LoVo cells were transplanted into nude mice. Microvessel density (MVD) was measured in nude mouse xenografts after intragastric administration of tetrandrine. RESULTS: Tetrandrine (2-8 microg/mL) inhibited the proliferation of HUVECs (24.6%-76.9%) and LoVo cells (11.6%-14.0%) after 48 h treatment. When HUVECs were incubated with 2-8 microg/mL tetrandrine, the number of tubules was reduced and the lumen lost its integrity after 24 h; the number of migrating HUVECs was decreased after 12 h as compared with the control group (P < 0.001). Furthermore, MVD was much less in LoVo cell xenografts treated with 80mg/kg tetrandrine than in those treated with normal saline (P = 0.035). CONCLUSIONS: Tetrandrine effectively suppresses angiogenesis in vitro, which may be through inhibiting cell proliferation, migration and tube-formation, inducing apoptosis and suppressing DNA synthesis of HUVECs. Tetrandrine also has an antiangiogenic effect on LoVo cell xenografts in nude mice.