Effect of hypoxia on HIF -1 α/MDR1/VEGF expression in gastric cancer cells treated with 5 -fluorouracil.
10.11817/j.issn.1672-7347.2022.210560
- Author:
Lu WANG
1
;
Wei XING
2
;
Jin QI
3
;
Yongyan LU
4
;
Linbiao XIANG
5
;
Yali ZHOU
6
Author Information
1. Department of Nuclear Medicine, Lanzhou University Second Hospital, Lanzhou 730030. wangl19@lzu.edu.cn.
2. Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou 730030.
3. Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou 730030.
4. First Clinical Medical College of Lanzhou University, Lanzhou 730030.
5. Second Clinical Medical College of Lanzhou University, Lanzhou 730030, China.
6. Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou 730030. zhouyali1956@163.com.
- Publication Type:Journal Article
- Keywords:
5-fluorouracil;
P-glycoprotein;
drug resistance;
hypoxia;
vascular endothelial growth factor
- MeSH:
Humans;
Fluorouracil/therapeutic use*;
Vascular Endothelial Growth Factor A/metabolism*;
Stomach Neoplasms/drug therapy*;
Drug Resistance, Multiple;
Vascular Endothelial Growth Factors/metabolism*;
Hypoxia;
ATP Binding Cassette Transporter, Subfamily B/genetics*;
ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics*;
Cell Line, Tumor;
Cell Hypoxia;
RNA, Messenger/metabolism*;
Hypoxia-Inducible Factor 1, alpha Subunit/genetics*;
Tumor Microenvironment
- From:
Journal of Central South University(Medical Sciences)
2022;47(12):1629-1636
- CountryChina
- Language:English
-
Abstract:
OBJECTIVES:Fluorouracil chemotherapeutic drugs are the classic treatment drugs of gastric cancer. But the problem of drug resistance severely limits their clinical application. This study aims to investigate whether hypoxia microenvironment affects gastric cancer resistance to 5-fluorouracil (5-FU) and discuss the changes of gene and proteins directly related to drug resistance under hypoxia condition.
METHODS:Gastric cancer cells were treated with 5-FU in hypoxia/normoxic environment, and were divided into a Normoxic+5-FU group and a Hypoxia+5-FU group. The apoptosis assay was conducted by flow cytometry Annexin V/PI double staining. The real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to detect the expression level of hypoxia inducible factor-1α (HIF-1α), multidrug resistance (MDR1) gene, P-glycoprotein (P-gp), and vascular endothelial growth factor (VEGF) which were related to 5-FU drug-resistance. We analyzed the effect of hypoxia on the treatment of gastric cancer with 5-FU.
RESULTS:Compared with the Normoxic+5-FU group, the apoptosis of gastric cancer cells treated with 5-FU in the Hypoxia+5-FU group was significantly reduced (P<0.05), and the expression of apoptosis promoter protein caspase 8 was also decreased. Compared with the the Normoxic+5-FU group, HIF-1α mRNA expression in the Hypoxia+5-FU group was significantly increased (P<0.05), and the mRNA and protein expression levels of MDR1, P-gp and VEGF were also significantly increased (all P<0.05). The increased expression of MDR1, P-gp and VEGF had the same trend with the expression of HIF-1α.
CONCLUSIONS:Hypoxia is a direct influencing factor in gastric cancer resistance to 5-FU chemotherapy. Improvement of the local hypoxia microenvironment of gastric cancer may be a new idea for overcoming the resistance to 5-FU in gastric cancer.
