摘要
目的研究解毒通利方对肺癌荷瘤小鼠肿瘤的抑制作用及对凋亡信号调节激酶(ASK)1/c-Jun氨基末端激酶(JNK)通路的调节作用。方法采用接种NCI-H358细胞法建立肺癌荷瘤小鼠模型,小鼠随机分为生理盐水组、解毒通利方低、中、高剂量组及顺铂组各6只,解毒通利方低、中、高剂量组分别按照10、20、40 g/kg(以生药含量计)灌胃给予小鼠解毒通利方,顺铂组按照5 mg/kg腹腔注射给予顺铂,生理盐水组灌胃给予生理盐水,1次/d,连续30 d,末次给药24 h后,分离肿瘤组织,测定肿瘤体积及重量,苏木素-伊红(HE)染色法检查肿瘤组织病理学,原位末端转移酶标记技术(TUNEL)染色测定肿瘤组织细胞凋亡率,实时定量聚合酶链式反应(RT-qPCR)及Western印迹测定肿瘤组织ASK1、JNK mRNA及蛋白水平,免疫组化法测定肿瘤组织ASK1及JNK的平均积分光密度(IOD)值。结果与生理盐水组比较,解毒通利方低、中、高剂量组及顺铂组肿瘤体积及重量显著降低,而肿瘤组织细胞凋亡率、肿瘤组织ASK1及JNK mRNA及蛋白水平、肿瘤组织ASK1及JNK免疫组化水平均显著升高(均P<0.05),小鼠肿瘤组织病理学改变明显。结论解毒通利方能够显著抑制肺癌荷瘤小鼠肿瘤组织生长,促进肿瘤细胞凋亡,其机制可能与调节ASK1/JNK通路有关。
Objective To study the inhibitory effect of Jiedu Tongli recipe on tumor of lung cancer tumor-bearing mice and regulation of apoptosis signal regulating kinase(ASK)1/c-Jun amino terminal kinase(JNK)pathway.Methods The model of lung cancer tumor-bearing mice was established by inoculating NCI-H358 cells.The mice were randomly divided into normal saline group,Jiedu Tongli recipe low,middle and high dose groups and cisplatin group,with 6 mice in each group.The mice in Jiedu Tongli recipe low,middle and high dose groups were given Jiedu Tongli prescription intragastrically according to 10,20 and 40 g/kg(in terms of crude drug content).Cisplatin group was intraperitoneally injected with 5 mg/kg cisplatin,normal saline group was given normal saline intraperitoneally,once a day for 30 d.24 h after the last administration,tumor tissue was separated,tumor volume and weight were measured,tumor histopathology was examined by hematoxylin-eosin(HE)staining,and apoptosis rate of tumor tissue was detected by in situ terminal transferase labeling(TUNEL)staining.The levels of ASK1,JNK mRNA and protein in tumor tissue were measured by real-time quantitative polymerase chain reaction(RT-qPCR)and Western blot,and the average integral optical density(IOD)of ASK1 and JNK in tumor tissue were measured by immunohistochemistry.Results Compared with normal saline group,the tumor volume and weight in low,middle and high dose groups of Jiedu Tongli recipe and cisplatin group were significantly decreased(P<0.05),while the apoptosis rate of tumor tissue,the mRNA and protein levels of ASK1 and JNK in tumor tissue and the immunohistochemical levels of ASK1 and JNK in tumor tissue were significantly increased(all P<0.05),the histopathological changes of tumor in mice were obvious.Conclusions Jiedu Tongli recipe could significantly inhibit the growth of tumor tissue and promote the apoptosis of tumor cells in lung cancer tumor-bearing mice,and its mechanism might be related to the regulation of ASK1/JNK pathway.
作者
吴亭
邱晓堂
邢明远
陈学武
蔡媛媛
WU Ting;QIU Xiao-Tang;XING Ming-Yuan(Department of Oncology,Hainan Hospital of Traditional Chinese Medicine,Haikou 570203,Hainan,China)
出处
《中国老年学杂志》
CAS
北大核心
2023年第9期2171-2176,共6页
Chinese Journal of Gerontology
基金
国家自然科学基金项目(81660550)
海南省基础与应用基础研究计划(省自然科学基金)(820QN408)。