溴苯基姜黄素对胆管癌细胞裸鼠移植瘤抑制作用及机制  

Inhibitory effect of bromophenyl curcumin on cholangiocarcinoma xenografts in nude mice and its mechanism

作　　者：赵冀安[1] 张梅 张蕊 董梁[4] 聂文佳[4] 刘文聪[5] 刘维丽[6] ZHAO Ji-An;ZHANG Mei;ZHANG Rui(Department of General Surgery,Hebei Medical University,Shijiazhuang 050013,Hebei,China)

机构地区：[1]河北医科大学第一医院普通外科,河北石家庄050013 [2]河北医科大学第一医院感染性疾病科,河北石家庄050013 [3]河北医科大学第一医院消化内科,河北石家庄050013 [4]河北医科大学第一医院医务处,河北石家庄050013 [5]河北医科大学第一医院超声科,河北石家庄050013 [6]河北医科大学第一医院肝胆外科,河北石家庄050013

出　　处：《中国老年学杂志》2022年第15期3720-3725,共6页Chinese Journal of Gerontology

基　　金：河北省医学科学研究重点科技研究计划资助项目(20190485)。

摘　　要：目的探讨姜黄素(CUR)衍生物溴苯基CUR(GL63)对人胆管癌细胞裸鼠移植瘤生长的抑制作用及机制。方法采用噻唑蓝(MTT)法检测GL63对人胆管癌RBE细胞增殖的影响;采用流式细胞法检测GL63对RBE细胞凋亡和周期的影响;建立人胆管癌裸鼠移植瘤模型,随机将裸鼠平均分为对照组、低浓度GL63组、高浓度GL63组各10只,分别给予生理盐水和10、20μmol/L GL63处理裸鼠。记录各组肿瘤重量和体积变化,并计算抑瘤率;对移植瘤组织进行病理学检测。Western印迹检测细胞中各蛋白表达情况。结果GL63能显著抑制人胆管癌RBE细胞生长,阻滞细胞周期于G0/G1期,诱导细胞发生凋亡,且呈浓度和时间依赖性。低、高浓度GL63组瘤重、瘤体积均明显小于对照组,抑瘤率明显高于对照组(P<0.05)。苏木素-伊红(HE)染色显示,低、高浓度GL63组肿瘤较对照组分化明显高,免疫组化显示,低、高浓度GL63组肿瘤细胞增殖抗原(PCNA)表达明显降低(P<0.05)。Western印迹结果显示,低、高浓度GL63组磷酸化酪氨酸激酶(p-JAK)2、磷酸化信号转导和转录活化因子(p-STAT)3蛋白表达与对照组相比显著下降(P<0.05)。下游通路中B细胞淋巴瘤(Bcl)-2、基质金属蛋白酶(MMP)-2、MMP-9蛋白表达明显下降,Bcl-2相关X蛋白(Bax)和组织金属蛋白酶抑制剂(TIMP)-2蛋白表达明显升高,且呈浓度依赖性(P<0.05)。结论GL63可促进胆管癌细胞凋亡,抑制其增殖和侵袭作用,从而抑制裸鼠移植瘤的生长。Objective To investigate the inhibitory effect of curcumin(CUR)analogue bromophenylcurcumin(GL63)on the growth of human cholangiocarcinoma cells in xenograft in nude mice and its mechanism.Methods The methyl thiazolyl tetrazolium(MTT)method and flow cytometry were used to examine the effects of bromophenylcurcumin on proliferation,apoptosis,cell cycle of RBE cells.A transplanted tumor model of human cholangiocarcinoma in nude mice was established,and the nude mice were randomly divided into the control group,the low-and the high-concentration GL63 group with 10 mice each,then saline and(10,20μmol/L)GL63 were used to treat the nude mice.The growth situations of transplanted tumor in different groups were recorded during the treatment,such as tumor weight,volumes,tumor inhibition rate.The pathology of tumor tissues in nude mice were examined.Western blot was used to detect the expression of various proteins in cells.Results GL63 could significantly inhibit proliferation activity of RBE cells,arrest cell cycle at G0/G1 phases and induce RBE cell apoptosis in concentration and time-dependent manner.The tumor weight and tumor volume of nude mice in the low-and the high-concentration GL63 group were significantly smaller than those in the control group,and the tumor inhibition rate was significantly higher than that in the control group.The low-and the high-concentration GL63 group had obviously higher differentiation with HE staining and significantly lower PCNA expression with immunohistochemistry than control group(P<0.05).Western blot showed that the expression of p-JAK2 and p-STAT3 protein in the low-and the high-concentration GL63 group were significantly lower than those in the control group(P<0.05).The expression of Bcl-2,MMP-2 and MMP-9 were significantly down-regulated while the expression of Bax and TIMP-2 were significantly up-regulated with a dose-dependent manner(P<0.05).Conclusions GL63 could inhibit the proliferation of cholangiocarcinoma cells,promote its apoptosis and invasion,thereby inhibiting the

关 键 词：裸鼠移植瘤 溴苯基姜黄素 胆管癌 JAK2/STAT3信号通路 

分 类 号：R735.8[医药卫生—肿瘤]