Study on HIF-1α regulating the sensitivity of 4-hydroxytamoxifen to breast cancer MCF-7 cells

Zongyue Chen; Jingyu Zhang; Minqin Zhang; Shuangqin Fan; Xiangchun Shen; Yan Chen; Yue Zhang

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Study on HIF-1α regulating the sensitivity of 4-hydroxytamoxifen to breast cancer MCF-7 cells

Author: Zongyue Chen ^{1
,

2} ; Jingyu Zhang ¹ ; Minqin Zhang ¹ ; Shuangqin Fan ¹ ; Xiangchun Shen ¹ ; Yan Chen ¹ ; Yue Zhang ¹
Author Information

1. Key Laboratory of Optimal Utilization of Natural Medicinal Resources, Guizhou Medical University ,Guiyang550025
2. Guiyang Healthcare Vocational University, GuiyangUniversity, Guiyang550081
Publication Type:Journal Article
Keywords: breast cancer; resistance; 4-hydroxy tamoxifen; hypoxia induced factor lα
From: Acta Universitatis Medicinalis Anhui 2022;57(6):938-943
CountryChina
Language:Chinese
Abstract: Objective:To explore the effect of hypoxia inducible factor 1α(HIF-1α)on tamoxifen resistance in breast cancer MCF-7,and to established a human breast cancer cell line(MCF-7/TR)with 4-hydroxy tamoxifen(4-OHT)resistance.
Methods:4-OHT was an active form of tamoxifenin vivo, resistant breast cancer cells MCF-7/TR were establishedin vitrousing 4-OHT. MTT assay was used to detect the effect of 4-OHT on the MCF-7 and MCF-7/TR cells, and the drug resistance multiple was detected. Western blot was used to detect the expression level of HIF-1α protein in MCF-7 and MCF-7/TR cells. The effects of HIF-1α inhibitor(LW6) or siRNA HIF-1α on MCF-7/TR cells and 4-OHT on MCF-7 cells treated with HIF-1α stabilizer(FG-4592) were detected by MTT and flow cytometry AV/PI staining.
Results:The results showed that the MCF-7/TR was successfully constructed, and the drug resistance ratio was(5.56±0.80). Compared with MCF-7 cells, MCF-7/TR cells had higher expression of HIF-1α protein and it was up-regulated after tamoxifen treatment. After giving LW6 or silencing the expression of HIF-1α,the down-regulation of HIF-1α expression enhanced the inhibitory effect of 4-OHT on MCF-7/TR cells. After treatment of FG-4592, the expression level of HIF-1α in breast cancer cells MCF-7 was up-regulated, and hindered the inhibition effect of tamoxifen on MCF-7 cells.
Conclusion:The above results indicate that HIF-1α plays an important role in 4-OHT resistant breast cancer, and targeting HIF-1α may be an effective way to increase the sensitivity of MCF7/TR cells to tamoxifen.
Full text:2025022115013213710HIF-1α调控4-羟基他...MCF-7细胞敏感性的研究_陈宗跃.pdf