基于MAPK通路探讨三虫通络散结方对Lewis肺癌小鼠的抑瘤作用  

Tumor inhibitory effects of Sanchong Tongluo Sanjie Formula on Lewis lung cancer mice based on MAPK pathway

作　　者：李阳[1] 张洽淳 陈蕾[1] 莫潘艳 黄国栋 王济国 曾超[1] LI Yang;ZHANG Qiachun;CHEN Lei;MO Panyan;HUANG Guodong;WANG Jigou;ZENG Chao(The Seventh Clinical College,Guangzhou University of Chinese Medicine,Shenzhen,Guangdong 518100,China)

机构地区：[1]广州中医药大学第七临床医学院,广东深圳518100

出　　处：《湖南中医药大学学报》2024年第12期2164-2171,共8页Journal of Hunan University of Chinese Medicine

基　　金：广东省中医药管理局项目(20231294);深圳市宝安区科创局项目(2021JD145);深圳市宝安区引进高层次医学团队项目资助项目(202403);深圳市宝安区2024年度区属公立医院高质量发展研究项目(BAGZL2024119)。

摘　　要：目的研究三虫通络散结方对Lewis肺癌小鼠的抑瘤作用及对丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路的调控作用。方法选取C57BL/6小鼠48只,随机挑选6只作为空白组;42只C57BL/6小鼠构建Lewis肺癌荷瘤小鼠模型,随机分为模型组(生理盐水)、阳性对照组(顺铂注射液2 mg/kg)、散剂低剂量组(三虫通络散结方散剂0.45 g/kg)、散剂高剂量组(三虫通络散结方散剂1.8 g/kg)、散剂低剂量+顺铂组(三虫通络散结方散剂0.45 g/kg+顺铂注射液2 mg/kg)、汤剂低剂量组(三虫通络散结方汤剂3.9 g/kg)、汤剂高剂量组(三虫通络散结方汤剂15.6 g/kg),每组6只,给药14 d后取材。计算抑瘤率和去瘤体质量;HE染色观察皮下移植瘤体、肺组织、肝组织的病理变化;qPCR检测皮下移植瘤细胞外调节蛋白激酶(extracellular regulated protein kinases,Erk)、缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)、p38、血管内皮生长因子A(vascular endothelial growth factor A,VEGFA)、c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)、基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)mRNA的表达量;Western blot检测皮下移植瘤Erk、HIF-1α、p38、VEGFA、JNK、MMP-2蛋白表达情况。结果(1)与模型组相比,阳性对照组、散剂低剂量+顺铂组、散剂高剂量组瘤体质量降低(P<0.05)。与散剂低剂量组相比,散剂高剂量组瘤体质量降低(P<0.05)。与阳性对照组相比,各中药单药组及模型组去瘤体质量升高(P<0.05)。(2)各组小鼠肺组织HE染色结果显示,散剂低剂量+顺铂组见较多肿瘤细胞坏死;各中药组细胞均少见核分裂,肿瘤转移灶较模型组少。各组小鼠肝组织HE染色结果显示,散剂低剂量+顺铂组、阳性对照组未见明显肿瘤病灶形成;散剂高剂量组、汤剂高剂量组的肿瘤转移灶体积相对较小。(3)与模型组相比,其余各荷瘤组皮下移植瘤组织中Erk、p38 mRNA表达下降(P<0.05),散剂低剂Objective To study the tumor inhibitory effects of Sanchong Tongluo Sanjie Formula(SCTLSJF)on Lewis lung cancer mice and its regulatory effects on the mitogen-activated protein kinase(MAPK)signaling pathway.Methods A total of 48 C57BL/6 mice were selected,and six of them were randomly assigned to the blank group.The remaining 42 C57BL/6 mice were used to establish the Lewis lung cancer-bearing mouse model,and were then randomized into model group(normal saline),positive control group(Cisplatin Injection 2 mg/kg),low-dose powder group(SCTLSJF powder 0.45g/kg),high-dose powder group(SCTLSJF powder 1.8 g/kg),low-dose powder+cisplatin group(SCTLSJF powder 0.45 g/kg+Cisplatin Injection 2 mg/kg),low-dose decoction group(SCTLSJF decoction 3.9 g/kg),and high-dose decoction group(SCTLSJF decoction 15.6 g/kg),with six mice in each group.Samples were collected 14 days after administration.The tumor suppression rate and tumor-free body mass were calculated.HE staining was used to observe the pathological changes of the subcutaneous xenograft tumor,lung tissues,and liver tissues;qPCR was employed to determine the mRNA expressions of extracellular regulated protein kinases(Erk),hypoxia inducible factor-1α(HIF-1α),p38 protein(p38),vascular endothelial growth factor A(VEGFA),c-Jun N-terminal kinase(JNK),and matrix metalloproteinase 2(MMP-2)in the subcutaneous xenograft tumor,while Western blot to examine the protein expressions of them.Results(1)Compared with the model group,the xenograft tumor mass in the positive control,low-dose powder+cisplatin,and high-dose powder groups was lower(P<0.05).Compared with the low-dose powder group,the xenograft tumor mass was lower in the high-dose powder group(P<0.05).Compared with the positive control group,the tumor-free body mass was higher in all pure Chinese medicine groups and model group(P<0.05).(2)The HE staining of lung tissues showed that the low-dose powder+cisplatin group exhibited a higher degree of tumor cell necrosis;in all pure Chinese medicine groups,nuclear division was ra

关 键 词：LEWIS肺癌细胞 三虫通络散结方 肺癌 MAPK信号通路 抑瘤作用 

分 类 号：R285.5[医药卫生—中药学]