蒿甲醚对小鼠结直肠癌的抑瘤及抗血管生成的实验研究

Experiment of inhibitive effect of artemether on colorectal cancer growth and angiogenesis in BALB/c mice

目的:探讨蒿甲醚(Artemether)对BALB/c小鼠CT-26结直肠癌的抑瘤及抗血管生成作用。方法:BALB/c小鼠皮下接种CT-26结直肠癌细胞(2×106mL-1)48只,雌、雄各半;随机分为6组,每组8只,分别为低剂量33.3mg/(kg·d)、中剂量50mg/(kg·d)、高剂量66.6mg/(kg·d)和中剂量50mg/(kg.d)加铁剂1.5mg/(kg·d)组、阳性对照组为顺铂5mg/(kg·d)、空白对照组为等体积生理盐水;均在接种5d后,顺铂采用腹腔注射15d停药,其余采用灌胃法持续给药15d,每天1次,末次给药24h后,处死动物。用Steel公式计算肿瘤体积V(mm3)=0.5ab2。采用免疫组化方法检测移植瘤组织微血管密度。结果:各治疗组抑瘤率分别为42.3%、51.4%、52.0%和53.5%;血管计数分别为13±6、31±4、38±5和11±9,生理盐水对照组为49±9;各治疗组微血管密度均明显低于生理盐水对照组(分别P<0.05,P<0.01);移植瘤体积较对照组显著减小。结论:在一定剂量范围内,口服蒿甲醚对小鼠CT-26结直肠癌移植瘤有明显的抑制作用;与铁剂合用能使抑瘤率增加;在具有抑瘤作用的同时,蒿甲醚还具有明显抑制小鼠结直肠癌移植瘤血管生成作用。

OBJECTIVE： To explore the inhibitive effect of artemether on colorectal cancer growth and angiogenesis in tumor bearing BALB/c mice. METHODS： Forty-eight （24 male and 24 female） BALB/c mice which were subcutaneous planted with CT-26 colorectal cell （2 × 10^6 mL^-1 ） were divided resourcefully into 6 groups, each group was 8 mice. They were low dose group with artemether of 33. 3 mg/（kg·d） as oral; middle dose group 50 mg/（kg· d）oral; high dose group 66.6 mg/（kg· d） oral; middle dose plus ferralia 50 mg/（kg· d）＋ 1.5 mg/（kg · d） oral;positive control group with DDP 5 mg/（kg ·d） ip and blank control group with normal saline as oral. The treatment started on day 1 and continued until day 15 and the mice were sacrificed 24 hours after last time. The volume of tumor was calculated following Steel＇s formula： V （mm^3） = 0.5 ab^2. The micro-vascular dense （MVD） was observed and countered under the microscopy by immunohistory chemistry. RESULTS：The inhibitive rates of artemether were 42. 3%, 51.4% and 52.0% ,respectively,and had a significant difference inhibitive effects on colorectal cancer growth （P= 0. 007, P= 0. 006, P= 0. 024 respectively）. The combination ferralia and Artemether synergenic the inhibitive effect on tumor bearing mice. The micro-vascular count value in different therapy groups respectively were 13 ± 6,31 ± 4,38±5 and 11±9, respectively and the normal saline control group was 49± 9. The microvascular denses （MVD） in different therapy groups were significant lower than that in the normal saline control group （P〈0. 05, P〈0.01, respectively）. CONCLUSIONS： Artemether has inhibitive effect on colorectal cancer growth in mice;The combination of ferralia and artemether has the synergenic inhibition effect. Meanwhile,artemether has also inhibitive effect on colorectal cancer angiogenesis in mice at the same of dosages.