BMP9 down-regulates HIF-1α to inhibit aerobic glycolysis,migration and invasion of breast cancer MDA-MB-231 cells
- VernacularTitle:BMP9下调HIF-1α抑制乳腺癌MDA-MB-231细胞的有氧糖酵解和迁移侵袭
- Author:
Tao YU
1
;
Yuan-Xiang CHEN
;
Shi-Yan LIU
;
Huo-Mei YU
;
De-Yu LIAO
;
Shi-Yu YANG
;
Tao ZENG
;
Lan WEI
;
Yan ZHANG
Author Information
- Keywords: breast cancer; BMP9; HIF-1α; aerobic glycolysis; migration; invasion
- From: Chinese Pharmacological Bulletin 2024;40(5):840-846
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the effects of bone-forming protein BMP9 on aerobic glycolysis,migration and invasion ability in triple-negative breast cancer MDA-MB-231 cells and the underlying mechanisms.Methods The experimental group infected MDA-MB-231 cells with human BMP9 recombinant adenovirus(AdBMP9),while the control group infected cells with empty GFP adenovirus.Lactate,glucose and ATP as-say kits were used to detect glucose uptake,lactate and ATP production.The correlation between BMP9 and key glycolytic enzyme genes in pancarcinoma was ana-lyzed using GEPIA2 database.The mRNA expression levels of GLUT1,HK2,PKM2 and LDHA in MDA-MB-231 cells after overexpression of BMP9 were detec-ted by qRT-PCR.Potential targets of BMP9 inhibiting MDA-MB-231 aerobic glycolysis were analyzed in STRING database.The expression levels of HIF-1αand downstream protein were detected by Western blot.The changes of cell migration and invasion ability after different treatments were evaluated by the scratch heal-ing assay and Transwell assay.Results Compared with the control group,BMP9 down-regulated glucose uptake,lactate production,ATP level(P＜0.01),and inhibited HIF-1α and its downstream protein ex-pression in MDA-MB-231 cells.Overexpression of HIF-1α in rescue experiment reversed the inhibitory effect of BMP9 on aerobic glycolysis,migration and in-vasion of MDA-MB-231 breast cancer cells.Conclu-sion BMP9 down-regulates HIF-1α to inhibit the aer-obic glycolysis and migration and invasion ability of MDA-MB-231 breast cancer cells.
