紫柏凝胶通过调节ERK及P38/MAPK信号通路下调宫颈癌荷瘤裸鼠E6、E7蛋白表达研究  

Zibai gel down-regulate E6,E7 protein expression in cervical cancer-bearing nude mice by regulating ERK and P38/MAPK signal pathways

作　　者：温利娟 薛晓鸥[2] 马秀丽[2] 米鑫 谢伟[2] WEN Lijuan;XUE Xiao’ou;MA Xiuli(Beijing Shunyi District Maternal and Child Health Hospital,Beijing 101300)

机构地区：[1]北京市顺义区妇幼保健院,北京101300 [2]北京中医药大学东直门医院,北京100700

出　　处：《陕西中医》2020年第5期589-592,604,共5页Shaanxi Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金资助面上项目(81774360);北京市科技计划课题G20工程支撑保障项目(Z151100003815014)。

摘　　要：目的:观察ERK及P38/MAPK信号通路在紫柏凝胶影响宫颈癌裸鼠移植瘤致癌蛋白E6、E7表达中的作用。方法:体外培养Siha细胞,成功建立人宫颈癌荷瘤裸鼠模型,随机分为模型组,顺铂组(腹腔内注射0.5 ml顺铂,4 d1次),紫柏凝胶高、中、低剂量组(外用紫柏凝胶0.9428、0.4714、0.2357 g/kg,1 d1次),试验期28 d。称取瘤重并测量瘤体积,HE染色观察移植瘤组织病理学变化,免疫组化SP法检测瘤体中的p-p38、p-ERK、E6及E7蛋白表达水平。结果:紫柏凝胶各组的裸鼠肿瘤体积均明显小于模型组(P<0.05),高、中、低剂量组抑瘤率分别为36.23%、31.24%和14.94%。HE染色紫柏凝胶各剂量组移植瘤组织出现明显坏死样改变。与模型组比较,高、中剂量紫柏凝胶组瘤组织的E6、E7蛋白表达水平降低(P<0.05),同时p-ERK及p-p38蛋白水平明显下降(P<0.05)。结论:紫柏凝胶对HPV(+)宫颈癌Siha细胞裸鼠移植瘤的生长具有明显抑制作用,可下调致癌蛋白E6和E7的表达,其机制可能与抑制ERK及P38/MAPK信号通路有关。Objective:To observe the role of ERK and P38/MAPK signaling pathway in the effect of Zibai gel on the expression of carcinogen E6 and E7 in nude mice with cervical cancer.Methods:The nude mice model of human cervical cancer bearing tumor was successfully established by culture of Siha cells in vitro.The nude mice were randomly divided into model group,cisplatin group(intraperitoneal injection of 0.5 ml of cisplatin,once every 4 days),high,medium and low dose groups(external use of Zibai gel 0.9428,0.4714,0.2357 g/kg,once a day)for 28 days.The tumor weight and the tumor volume were measured.The pathological changes of the tumor tissue were observed by HE staining.The levels of p-p38,p-ERK,E6 and E7 proteins in the tumor were detected by mmunohistochemical SP method.Results:Nude mice tumor volume of Zibai gel groups were significantly less than model group(P<0.05),inhibitory rate of high,medium and low dose group were 36.23%,31.24%and 14.94%.HE staining showed significant changes in tumor tissue of nude mice.Compared with the model group,the expression of E6 and E7 protein in tumor tissue of high and middle dose Zibai gel group decreased(P<0.05),while the levels of p-ERK and p-p38 protein decreased significantly(P<0.05).Conclusion:Zibai gel has obvious effect on cervical cancer growth in nude mice transplanted by HPV(+)Siha cells,Zibai gel can down-regulate the expression of carcinogenic proteins E6 and E7.The mechanism may be related to the inhibition of ERK and P38/MAPK signaling pathway.

关 键 词：紫柏凝胶 裸鼠 SIHA细胞 信号通路 致癌蛋白 HE染色 

分 类 号：R711.74[医药卫生—妇产科学]