2-十二烷基-6-甲氧基-2,5-二烯-1,4-环己二酮对Lewis肺癌小鼠的抑瘤作用研究  

Tumor inhibitory effect of 2-dodecyl-6-methoxy-2,5-diene-1,4-cyclohexanedione on Lewis lung cancer mice

作　　者：张晓萍 王誉湘 谢静晓 王璐 陈秋燕 陈林倩 刘林[1] 钟怡颖 黄仁彬[1] Zhang Xiaoping;Wang Yuxiang;Xie Jingxiao;Wang Lu;Chen Qiuyan;Chen Linqian;Liu Lin;Zhong Yiying;Huang Renbin(Pharmaceutical College,Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学药学院,南宁530021

出　　处：《广西医科大学学报》2023年第6期930-937,共8页Journal of Guangxi Medical University

基　　金：国家自然科学基金资助项目(No.81760665);广西生物靶向诊治研究重点实验室开放课题项目(No.GXSWBX201804)。

摘　　要：目的:研究杨桃根提取物2-十二烷基-6-甲氧基-2,5-二烯-1,4-环己二酮(DMDD)对Lewis肺癌小鼠的抑瘤作用及其可能机制。方法:以C57BL/6小鼠构建Lewis肺癌小鼠皮下移植瘤模型,随机分为模型组、顺铂组和DMDD低、中、高剂量组,每组8只。给药14 d后,计算抑瘤率和脏器指数。采用酶联免疫吸附试验(ELISA)法检测移植瘤组织中炎症因子[白介素-1β(IL-1β)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)]水平,苏木精-伊红(HE)染色法观察移植瘤组织病理学改变,western blotting法检测移植瘤组织B-淋巴细胞瘤基因-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、核因子(NF)-κB p65(p65)和磷酸化p65(p-p65)蛋白表达水平。结果:DMDD低、中、高剂量组和顺铂组瘤体生长缓慢,抑瘤率分别为51.08%、39.81%、46.92%、56.98%。DMDD高剂量组肺脏指数、脾脏指数与模型组比较,差异均有统计学意义(P<0.01)。与模型组比较,DMDD各剂量组IL-1β、IL-6、TNF-α水平均降低(P<0.05)。给予DMDD后坏死区域明显,细胞排列疏松,细胞核固缩。与模型组比较,DMDD中、高剂量组和顺铂组Bcl-2蛋白相对表达量明显降低(P<0.05),DMDD各剂量组和顺铂组Bax蛋白相对表达量升高,而p-p65/p65比值显著降低(均P<0.05)。结论:DMDD可抑制Lewis肺癌小鼠肿瘤生长,可能通过调控NF-κB信号通路诱导肺癌细胞凋亡,从而发挥抗肿瘤作用。Objective:To study the tumor inhibitory effect of 2-dodecyl-6-methoxy-2,5-diene-1,4-cyclohexanedione(DMDD)isolated from the root of Averrhoa carambola L.on Lewis lung cancer mice and its possible mechanism.Methods:A subcutaneous transplantation tumor model of Lewis lung cancer mice was constructed with C57BL/6 mice and randomly divided into model group,cisplatin group,low-dose DMDD group,mediumdose DMDD group and high-dose DMDD group,with 8 mice in each group.After 14 days of administration,tumor inhibitory rate and organ index were calculated.The levels of inflammatory factors[interleukin-1(IL-1),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)]in transplanted tumor tissues were detected by enzymelinked immunosorbent assay(ELISA).Hematoxylin-eosin(HE)staining was used to observe the pathological changes of transplanted tumor tissue,and western blotting was used to detect B-cell lymphoblastoma gene-2(Bcl-2),Bcl-2-associated X protein(Bax),nuclear factor(NF)-κB p65(p65)and phosphorylated p65(p-p65)protein expression levels in tumor tissues.Results:The tumor growth was slow in all DMDD groups and the cisplatin group,and the tumor inhibitory rates were 51.08%,39.81%,46.92%and 56.98%,respectively.There were statistically significant differences in the lung index and spleen index between the DMDD high-dose group and the model group(P<0.01).Compared with the model group,the levels of IL-1,IL-6 and TNF-αin all DMDD groups decreased(P<0.05).After administra-tion of DMDD,the necrotic area was obvious,the cell arrangement was loose,and the nucleus was solidified.Compared with the model group,the relative expression levels of Bcl-2 protein in medium-dose and high-dose DMDD groups significantly decreased,as well as the cisplatin group(P<0.05),the relative expression levels of Bax protein in all DMDD dose groups and the cisplatin group increased,while the P-P65/p65 ratio significantly decreased(all P<0.05).Conclusion:DMDD can inhibit tumor growth in Lewis lung cancer mice,possibly by regulating the NF-κB signaling p

关 键 词：2-十二烷基-6-甲氧基-2 5-二烯-1 4-环己二酮 肺癌 细胞凋亡 NF-ΚB信号通路 

分 类 号：R963[医药卫生—微生物与生化药学]