摘要
目的研究考布他汀A-4(CA4)衍生物SIPI 0385-1的抗肿瘤作用并探索其作用机制。方法采用四甲基偶氮唑盐比色(MTT)法研究SIPI 0385-1对人恶性黑色素瘤细胞株A375、人表皮癌细胞株A431、人肺癌细胞株A549、人乳腺癌细胞株Bcap-37、人低分化胃腺癌细胞株BGC-823、人大细胞肺癌细胞株NCI-H460、人乳腺癌细胞株MCF-7、人肝癌细胞细胞株QGY-7701、小鼠黑色素瘤细胞株K111和小鼠白血病细胞株L1210生长的抑制作用;采用小鼠B 16黑色素模型及人肺腺癌A549和人低分化胃腺癌BGC-823裸鼠移植瘤模型研究SIPI 0385-1体内抗肿瘤活性;采用鸡胚绒毛尿囊膜(CAM)模型研究SIPI 0385-1对新生血管的影响。结果体外试验表明,除NCI-H460和MCF-7细胞株外,SIPI 0385-1对其他各供试细胞株的IC50值均大于100μg/ml,对体外肿瘤细胞无抑制作用。体内试验表明,25、75和225 mg/kg SIPI 0385-1对小鼠黑色素瘤B 16的抑制率分别为52.10%、52.47%和63.48%;对裸鼠异种移植人肺腺癌A549实体瘤和人低分化胃腺癌BGC-823实体瘤的抑制率分别为43.62%、54.61%、66.92%和40.55%、50.67%和67.17%,与对照组相比,差异均具有统计学意义(P<0.05)。SIPI 0385-1可明显减少CAM上的血管数目,血管生成抑制率为52%,与对照组相比,差异具有统计学意义(P<0.01)。结论SIPI 0385-1具有良好的抗肿瘤作用,其作用机制可能是抑制肿瘤血管的生成。
Objective To investigate the anti-cancer effect of combretastatin A-4(CA4) derivative SIPI 0385-1 and its mechanism.Methods The anti-proliferative effects of SIPI 0385-1 were analyzed on A375,A431,A549,Bcap-37,BGC-823,NCI-H460,MCF-7,QGY-7701,K111 and L1210 cell lines by MTT assay.The mouse model of B16 melanoma,nudemouse model of A549 lung cancer and BGC-823 gastric cancer were used to evaluate the anti-cancer effect of SIPI 0385-1 in vivo.Chicken chorioallantoic membrane(CAM) inhibition test were used to study the mechanism of SIPI 0385-1 on inhibiting tumor angiogenesis.Results Except NCI-H460 and MCF-7 cells,the IC50 values of SIPI 0385-1 against all other cells were above 100 μg/ml.The tumor growth inhibition rate caused by intravenous injection of SIPI 0385-1(25,75 and 225 mg/kg/d) were 52.10%,52.47%,63.48%;43.62%,54.61%,66.92% and 40.55%,50.67%,67.17% respectively in mouse model of B16 melanoma,nude mouse model of A549 lung cancer and BGC-823 gastric cancer.The differences were significant compared with control group(P<0.05).The inhibition of SIPI 0385-1 on CAM test was 52%,the differences were significant compared with control group(P<0.01).Conclusion SIPI 0385-1 has remarkable anti-cancer effect and its mechanism may be to inhibit tumor angiogenesis.
出处
《世界临床药物》
CAS
2016年第4期241-245,共5页
World Clinical Drug
