大黄素联合甲磺酸阿帕替尼通过上调ACE2-Ang(1-7)-Mas受体轴抑制胰腺癌细胞增殖的研究  

Inhibition of Emodin Combined with Apatinib Mesylate on Proliferation of Pancreatic Cancer Cells by Up-Regulating the ACE2-Ang(1-7)-Mas Receptor Axis

作　　者：王婧[1] 马晓 尚昆[1] 林海珊[1] 曹邦伟[1] WANG Jing;Ma Xiao;SHANG Kun;LIN Haishan;CAO Bangwei(Dept.of Oncology,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China)

机构地区：[1]首都医科大学附属北京友谊医院肿瘤科,北京100050

出　　处：《中国医院用药评价与分析》2021年第3期269-272,共4页Evaluation and Analysis of Drug-use in Hospitals of China

基　　金：北京市临床重点专科(2018-2020);北京市医院管理中心消化内科学科协同发展中心专项经费资助(No.XXT01);首都卫生发展科研专项基金资助(No.2018-2-2022);首都医科大学科研培育基金(No.PYZ20148)。

摘　　要：目的:验证大黄素联合甲磺酸阿帕替尼通过上调血管紧张素转换酶2(ACE2)-血管紧张素(1-7)[Ang(1-7)]-Mas受体轴抑制胰腺癌细胞增殖的作用及机制。方法:采用四甲基偶氮唑盐(methyl thiazolyl tetrazolium,MTT)比色法检测大黄素、甲磺酸阿帕替尼以及联合用药(大黄素+甲磺酸阿帕替尼)对胰腺癌PANC-1细胞增殖能力的影响,以空白处理作为对照。采用酶联免疫吸附试验测定细胞上清液白细胞介素6(IL-6)、Ang(1-7)水平。采用Western blot法和免疫荧光方法检测各实验组细胞ACE2、Mas受体蛋白表达情况。结果:加药干预细胞后,大黄素组细胞抑制率为11.72%,甲磺酸阿帕替尼组的抑制率为15.94%,联合用药组的抑制率为28.84%,联合用药组显著高于单药组,差异均有统计学意义(P<0.05)。甲磺酸阿帕替尼组IL-6水平明显低于大黄素组,联合用药组明显低于大黄素组及甲磺酸阿帕替尼组;与IL-6相反,大黄素组、甲磺酸阿帕替尼组及联合用药组的Ang(1-7)水平明显高于对照组,其中联合用药组最高,上述差异均有统计学意义(P<0.01)。Western blot法及免疫荧光方法检测结果表明,大黄素组及甲磺酸阿帕替尼组ACE2及Mas受体蛋白表达水平高于对照组,联合用药组表达最高。结论:大黄素及甲磺酸阿帕替尼单药通过上调ACE2-Ang(1-7)-Mas受体轴抑制胰腺癌细胞增殖,两药联合应用具有协同效应。OBJECTIVE:To verify the effect and mechanism of emodin combined with apatinib mesylate in inhibiting the proliferation of pancreatic cancer cells by up-regulating the angiotensin converting enzyme 2(ACE2)-Angiotensin(1-7)[Ang(1-7)]-Mas receptor.METHODS:Methyl Thiazolyl Tetrazolium(MTT)was used to detect the effects of emodin,apatinib mesylate and drug combination(emodin+apatinib mesylate)on the proliferation of PANC-1 cells.Without medicine were took as the control.Enzyme-linked immunosorbent assay was used to determine the levels of interleukin 6(IL-6)and Ang(1-7)in the cell supernatant.Western blot method and immunofluorescence method were used to detect the expression of ACE2 and Mas receptor protein in each experimental group.RESULTS:After intervention,the cell inhibition rate of the emodin group,apatinib mesylate group and drug combination group was respectively 11.72%,15.94%and 28.84%,the drug combination group was significantly higher than the single drug group,the differences were statistically significant(P<0.05).The level of IL-6 in the apatinib mesylate group was significantly lower than that in the emodin group,and that in the drug combination group was significantly lower than that in the emodin group and the apatinib mesylate group.In contrast to the level of IL-6,Ang(1-7)in the emodin group,apatinib mesylate group and combination group was significantly higher than that in the control group,and the drug combination group had the highest Ang(1-7),with statistically significant difference(P<0.01).The results of Western blot and immunofluorescence showed that the expression levels of ACE2 and Mas receptor protein in the emodin group and apatinib mesylate group were higher than those in the control group,and the expression levels of ACE2 and Mas receptor protein in the drug combination group were the highest.CONCLUSIONS:The monotherapy of emodin and apatinib mesylate inhibits the proliferation of pancreatic cancer cells by up-regulating the ACE2-Ang(1-7)-Mas receptor axis,and the combination of two dru

关 键 词：大黄素 甲磺酸阿帕替尼 胰腺癌 血管紧张素转换酶2 血管紧张素(1-7) 

分 类 号：R979.1[医药卫生—药品]