[1]李永真,王志慧,李　娜,等.磷脂酰肌醇-3-激酶/蛋白激酶B和丝裂原活化蛋白激酶/细胞信号调节激酶1/2信号通路抑制剂对乳腺癌细胞缺氧诱导因子-2α表达的影响[J].新乡医学院学报,2021,38(4):308-312.[doi:10.7683/xxyxyxb.2021.04.002]
　LI Yongzhen,WANG Zhihui,LI Na,et al.Effects of phosphatidylinositol-3-kinase/protein kinase B and mitogen activated protein kinase/cell signal regulated kinase 1/2 signaling pathways inhibitors on the expression of hypoxia inducible factor-2α in breast cancer cells[J].Journal of Xinxiang Medical University,2021,38(4):308-312.[doi:10.7683/xxyxyxb.2021.04.002]
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磷脂酰肌醇-3-激酶/蛋白激酶B和丝裂原活化蛋白激酶/细胞信号调节激酶1/2信号通路抑制剂对乳腺癌细胞缺氧诱导因子-2α表达的影响
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
38
期数:
2021年4
页码:
308-312
栏目:
基础研究
出版日期:
2021-04-05

文章信息/Info

Title:
Effects of phosphatidylinositol-3-kinase/protein kinase B and mitogen activated protein kinase/cell signal regulated kinase 1/2 signaling pathways inhibitors on the expression of hypoxia inducible factor-2α in breast cancer cells
作者:
李永真1; 王志慧1; 2; 李　娜1; 宋　颖1; 韩正华3; 千新来1; 原志庆1; 陆漫漫1; 李思琦1
（1.新乡医学院病理学系，河南　新乡　453003；2.新乡医学院第三附属医院，河南　新乡　453003；3.新乡医学院三全学院，河南　新乡　453003）
Author(s):
LI Yongzhen1; WANG Zhihui1; 2; LI Na1; SONG Ying; HAN Zhenghua3; QIAN Xinlai1; YUAN Zhiqing1; LU Manman1; LI Siqi1
(1.Department of Pathology,Xinxiang Medical University,Xinxiang 453003,Henan Province,China 2.Department of Pathdogy,the Third Affiliated Hospital of Xinxiang Medical University,Xinxiang 453003,Henan Province,China；3.College of Sanquan,Xinxiang Medical University,Xinxiang 453003,Henan Province,China)
关键词:
乳腺癌; 缺氧诱导因子-2α; 磷脂酰肌醇-3-激酶/蛋白激酶B通路; 丝裂原活化蛋白激酶/细胞信号调节激酶1/2信号通路
Keywords:
breast cancer hypoxia inducible factor-2α phosphatidylinositol-3-kinase/protein kinase B pathway mitogen activated protein kinase/cell signal regulated kinase 1/2 signaling pathway
分类号:
R737.9
DOI:
10.7683/xxyxyxb.2021.04.002
文献标志码:
A
摘要:
目的　探讨磷脂酰肌醇-3-激酶/蛋白激酶B（PI3K/Akt）和丝裂原活化蛋白激酶/细胞信号调节激酶1/2（MEK/ERK1/2）信号通路抑制剂对缺氧诱导的乳腺癌MCF-7细胞中缺氧诱导因子-2α（HIF-2α）表达的影响。方法　乳腺癌 MCF-7细胞常规培养24 h后，分为常氧组、缺氧组、缺氧+低剂量LY294002组、缺氧+高剂量LY294002组，缺氧+低剂量U0126组和缺氧+高剂量U0126组。常氧组细胞使用含生理盐水的RPMI 1640 培养基，缺氧组细胞使用含100 μmol·L-1氯化钴的RPMI 1640 培养基，缺氧+低剂量LY294002组细胞使用含100 μmol·L-1氯化钴和4 μmol·L-1 LY294002的RPMI 1640 培养基，缺氧+高剂量LY294002组细胞使用含100 μmol·L-1氯化钴和40 μmol·L-1 LY294002的RPMI 1640 培养基，缺氧+低剂量U0126组细胞使用含100 μmol·L-1氯化钴和2 μmol·L-1 U0126的 RPMI 1640 培养基，缺氧+高剂量U0126组细胞应用含8 μmol·L-1 U0126的RPMI 1640 培养基，继续培养3 h。采用实时荧光定量聚合酶链式反应检测各组细胞HIF-2α mRNA的表达；采用Western blot法检测各组细胞HIF-2α蛋白、磷酸化Akt（P-Akt）和磷酸化ERK1/2（P-ERK1/2）蛋白的表达。结果　缺氧组细胞中HIF-2α mRNA相对表达量及HIF-2α蛋白、p-Akt蛋白和p-ERK1/2蛋白相对表达量高于常氧组（PPPP<0.05）。>结论　PI3K/Akt和MEK/ERK1/2信号通路可能是缺氧诱导HIF-2α表达的上游信号通路，在缺氧条件下对 HIF-2α具有正向调节作用，在乳腺癌的发生、发展中发挥重要作用。
Abstract:
Objective　To investigate the effects of phosphatidylinositol-3-kinase/protein kinase B（PI3K/Akt） and mitogen activated protein kinase/cell signal regulated kinase 1/2（MEK/ERK1/2） signaling pathways inhibitors on the expre-ssion of hypoxia inducible factor-2α（HIF-2α）in hypoxia-induced breast cancer MCF-7 cells.Methods　　The breast cancer MCF-7 cells after routinely cultured for 24 h were divided into normoxia group,hypoxia group,hypoxia + low-dose LY294002 group,hypoxia + high-dose LY294002 group,hypoxia + low-dose U0126 group and hypoxia + high-dose U0126 group.The cells in the normoxia group were cultured with RPMI 1640 medium containing normal saline,the cells in the hypoxia group were cultured with RPMI 1640 medium containing 100 μmol·L-1 CoCl2,the cells in the hypoxia + low-dose LY294002 group were cultured with RPMI 1640 medium containing 100 μmol·L-1 CoCl2 and 4 μmol·L-1 LY294002,the cells in the hypoxia + high-dose LY294002 group were cultured with RPMI 1640 medium containing 100 μmol·L-1 CoCl2 and 40 μmol·L-1 LY294002,the cells in the hypoxia + low-dose U0126 group were cultured with RPMI 1640 medium containing 100 μmol·L-1 CoCl2 and 2 μmol·L-1 U0126,and the cells in the hypoxia + high-dose U0126 group were cultured with RPMI 1640 medium containing 100 μmol·L-1 CoCl2 and 8 μmol·L-1 U0126,the culture was continued for 3 h.The expression of HIF-2α mRNA was detected by real-time quantitative polymerase chain reaction,the expression of HIF-2α protein,Phosphorylated Akt (P-Akt) protein and phosphorylated ERK1/2(P-ERK1/2) protein were detected by Western blot.Results　The relative expression levels of HIF-2α mRNA,HIF-2α protein,P-Akt protein and p-ERK1/2 protein in the hypoxia group were higher than those in the normoxia group (P<0.05);the relative expression levels of HIF-2α mRNA,HIF-2α protein,P-Akt protein and p-ERK1/2 protein in the hypoxia + low-dose LY294002 group,hypoxia + high-dose LY294002 group,hypoxia + low-dose U0126 group and hypoxia + high-dose U0126 group were lower than those in the hypoxia group (P<0.05).The relative expression levels of HIF-2α mRNA,HIF-2α protein,P-Akt protein and p-ERK1/2 protein in the hypoxia + high-dose LY294002 group were lower than those in the hypoxia + low-dose LY294002 group (P<0.05);the relative expression levels of HIF-2α mRNA,HIF-2α protein,P-Akt protein and p-ERK1/2 protein in the hypoxia + high-dose U0126 group were lower than those in the hypoxia + low-dose U0126 group (P<0.05).Conclusion　PI3K/Akt and MEK/ERK1/2 signaling pathways may be upstream signaling pathways of HIF-2α expression induced by hypoxia,they have a positive regulatory effect on HIF-2α under hypoxia conditions,and play an important role in the occurrence and development of breast cancer.

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更新日期/Last Update: 2021-04-05