槲皮素对子宫颈癌荷瘤小鼠移植瘤生长的影响及其机制  

Effects of quercetin on the growth of transplanted tumor in mice with cervical cancer and its mechanism

作　　者：脱淑梅[1] 张彦骅[2] 党云[1] 脱勋员 龙丽霞[1] TUO Shu-mei;ZHANG Yan-hua;DANG Yun;TUO Xun-yuan;LONG Li-xia(Department of Gynecologic Oncology,Gansu Provincial Maternal and Child Health Hospital,Lanzhou 730050,Gansu Province,China;Department of Gynecologic,Gansu Provincial Maternal and Child Health Hospital,Lanzhou 730050,Gansu Province,China)

机构地区：[1]甘肃省妇幼保健院妇瘤科,甘肃兰州730050 [2]甘肃省妇幼保健院妇一科,甘肃兰州730050

出　　处：《中国临床药理学杂志》2021年第2期150-152,156,共4页The Chinese Journal of Clinical Pharmacology

基　　金：甘肃省卫生行业科研管理项目(GSWSXY-2019-94);甘肃省青年科技研究基金项目(1506RJYA161)。

摘　　要：目的探讨槲皮素对子宫颈癌荷瘤小鼠移植瘤的抗肿瘤作用,并分析其作用机制。方法将Hela细胞接种于裸鼠皮下建立人宫颈癌裸鼠皮下移植瘤模型,将荷瘤小鼠随机分为模型组、阳性对照组、实验组,每组10只。连续给药14 d后,计算肿瘤体积及抑瘤率,用原位末端转移酶标记技术(TUNEL)检测肿瘤细胞凋亡情况,用蛋白质印迹法检测蛋白激酶R样内质网激酶(PERK)、磷酸化蛋白激酶R样内质网激酶(p-PERK)、真核起始因子2α(eIF 2α)、磷酸化eIF2α(p-eIF2α)、转录激活因子4(ATF4)、C/EBP同源蛋白(CHOP)蛋白表达水平。结果模型组、阳性对照组和实验组小鼠的肿瘤体积分别为(1.53±0.20),(1.04±0.31),(1.12±0.37)cm3;模型组、阳性对照组和实验组肿瘤细胞凋亡率分别为0,(48.39±7.51)%,(45.44±6.20)%;模型组、阳性对照组和实验组PERK蛋白相对表达水平分别为0.74±0.15,0.61±0.23,0.50±0.14;模型组、阳性对照组和实验组p-PERK蛋白相对表达水平分别为0.65±0.09,1.02±0.20,1.64±0.12;模型组、阳性对照组和实验组eIF2α蛋白相对表达水平分别为0.66±0.11,0.40±0.21,0.42±0.18;模型组、阳性对照组和实验组p-eIF2α蛋白相对表达水平分别为0.58±0.13,1.15±0.25,1.30±0.17;模型组、阳性对照组和实验组ATF4蛋白相对表达水平分别为0.31±0.06,0.53±0.05,0.72±0.09;模型组、阳性对照组和实验组CHOP蛋白相对表达水平分别为0.26±0.07,0.39±0.04,0.63±0.10,模型组与阳性对照组比较或实验组和模型组比较,上述指标的差异均有统计学意义(均P<0.05)。结论槲皮素对人宫颈癌移植瘤的生长具有明显的抑制作用,其机制与通过诱导PERK和eIF2α蛋白磷酸化,上调ATF4及CHOP表达,激活内质网应激有关。Objective To investigate the anti-tumor effect of quercetin on the growth of transplanted tumor in mice with cervical cancer and analyze its mechanism.Methods Hela cells were inoculated subcutaneously in mice to establish the subcutaneously transplanted tumor model of human cervical cancer,and the tumor-bearing mice were randomly divided into the model group,positive control group and experimental group,with 10 mice in each group.After 14 days of continuous administration,tumor volume and inhibitory rate were calculated.TUNEL was used to detect apoptosis of tumor cells.The expression levels of protein kinase RNA-like endoplasmic reticulum kinase(PERK),phospho-PERK(p-PERK),eukaryotic initiation factor 2α(eIF2α),phosphorylated eIF2α(p-eIF2α),activating transcription factor 4(ATF4),and C/EBP homologous protein(CHOP)were detected by Western blot.Results The tumor volume in model group,positive control group and experimental group were(1.53±0.20),(1.04±0.31),(1.12±0.37)cm3;the apoptosis rate of tumor cells in the above three groups were 0,(48.39±7.51)%,(45.44±6.20)%;the levels of PERK in the above three groups were 0.74±0.15,0.61±0.23,0.50±0.14;the levels of p-PERK in the above three groups were 0.65±0.09,1.02±0.20,1.64±0.12;the levels of eIF2αin the above three groups were 0.66±0.11,0.40±0.21,0.42±0.18;the levels of p-eIF2αin the above three groups were 0.58±0.13,1.15±0.25,1.30±0.17;the levels of ATF4 in the above three groups were 0.31±0.06,0.53±0.05,0.72±0.09;and the levels of CHOP in the above three groups were0.26±0.07,0.39±0.04,0.63±0.10.There were significant difference of the factors between model group and positive control group or experimental group and model group,(all P<0.05).Conclusion Quercetin can significantly inhibit the growth of cervical carcinoma transplant tumor by inducing the phosphorylation of PERK and eIF2αproteins,and upregulating the expression of ATF4 and CHOP.

关 键 词：子宫颈癌 槲皮素 蛋白激酶R样内质网激酶 真核起始因子2α 转录激活因子4 C/EBP同源蛋白 

分 类 号：R28[医药卫生—中药学]