摘要
目的建立人肺癌裸鼠皮下与原位移植瘤模型,比较地高辛对两种模型抗肿瘤作用的差异,初步探讨地高辛抗肺癌的机制。方法裸鼠皮下接种H460组织块建立皮下移植瘤模型后,测量肿瘤体积,瘤组织行HE染色和免疫组化检测;将H460-Luc细胞悬液穿刺注射到裸鼠肺部建立原位移植瘤模型,活体成像并记录荧光值,解剖后观察裸鼠脏器肿瘤病灶。结果与对照组相比,皮下移植模型中吉西他滨组有明显抑瘤效果(P<0.05),地高辛各剂量组均无明显抑瘤效果(P>0.05);各给药组的肿瘤细胞排列密度降低,坏死、纤维增生明显,并且p-p38、p-ERK、Nur77蛋白表达明显增高;原位移植模型中,吉西他滨和地高辛中(P<0.05)、低剂量组均有抑瘤效果,但地高辛高剂量组加速肿瘤发展(P<0.05)。结论地高辛对原位移植瘤敏感性优于皮下移植瘤,可能通过上调肿瘤组织的p-p38、p-ERK、Nur77蛋白的表达来抑制肿瘤生长。
Aim To establish subcutaneous and orthotopic transplantation models of human lung cancer in nude mice,and compare the anti-cancer effects of digoxin between the two models.Methods After subcu-taneous inoculation of H460 tissues in nude mice,the tumor volume was measured;HE staining and immunohistochemistry were performed;H460-Luc cell suspension was injected into the lung of nude mice toestablish orthotopic tumor model,the in vivo imaging and fluorescence values were recorded,and the tumor lesions in other organs were observed after dissection.Results Compared with control group,the gemcitabine group had a significant anti-tumor effect(P<0.05),and digoxin groups had no significant difference(P>0.05).HE staining showed that the cell density in each treatment group decreased,and necrosis and/or fibrous hyperplasia were obvious.Immunohistochemistry indicated that the protein expression of p-p38,p-ERK and Nur77 in each treatment group significantly increased in the subcutaneous transplantation model;in the orthotopic transplantation model,the gemcitabine,the middle(P<0.05)and low dose of digoxin group could inhibit the tumor growth,while the high dose of digoxin group accelerated the development of tumor(P<0.05).Conclusion Digoxin is more sensitive to orthotopic transplanted tumor than subcutaneous transplanted tumor,anddigoxin may inhibit the tumor growth by up-regulating the expression of p-p38,p-ERK and Nur77.
作者
王佳南
汪紫易
卢洪胜
陈浩轩
陶玲珑
王峥涛
陈晨
汪旭明
胡琼莹
WANG Jia-nan;WANG Zi-yi;LU Hong-sheng;CHEN Hao-xuan;TAO Ling-long;WANG Zheng-tao;CHEN Chen;WANG Xu-ming;HU Qiong-ying(School of Medicine,Taizhou University,Taizhou,Zhejiang 318000,China;School of Medicine,Ningbo University,Ningbo,Zhejiang 315000,China;Taizhou Central Hospital(Taizhou University Hospital),Taizhou,Zhejiang 318000,China;Taizhou Municipal Hospital,Taizhou,Zhejiang 318000,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2021年第11期1571-1577,共7页
Chinese Pharmacological Bulletin
基金
浙江省基础公益研究计划项目(NoLGF21H280002,2016C37143)
台州市科技项目(No15yw07,1902ky44)。
关键词
肺癌
原位移植模型
皮下移植模型
地高辛
P38
ERK
Nur77
lung cancer
orthotopic transplantation model
subcutaneous transplantation model
digoxin
p38
ERK
Nur77
