Effect of Chaihu Guizhitang on Triple-negative Breast Cancer Cells: Based on HIF-1α/VEGFA Signaling Pathway
10.13422/j.cnki.syfjx.20230321
- VernacularTitle:基于HIF-1α/VEGFA信号通路探讨柴胡桂枝汤对三阴性乳腺癌细胞的影响
- Author:
Yuxiao FANG
1
;
Shumei WANG
1
;
Lingli LIU
1
;
Ning WEI
1
;
Haoyao PAN
1
;
Guangyao JIAN
1
;
Xinyi LI
1
Author Information
1. College of Traditional Chinese Medicine (TCM), Chongqing Key Laboratory of TCM for Prevention and Cure of Metabolic Diseases, Chongqing Medical University, Chongqing 400016, China
- Publication Type:Journal Article
- Keywords:
Chaihu Guizhitang;
triple-negative breast cancer (TNBC);
hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor A (VEGFA) signaling pathway;
angiogenesis
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(4):18-24
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effect of Chaihu Guizhitang on triple-negative breast cancer (TNBC) cells based on hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor A (VEGFA) signaling pathway. MethodTNBC xenograft model was established and the cells were randomized into model group, capecitabine group (0.2 mg·kg-1), Chaihu Guizhitang low-dose group, medium-dose group, and high-dose group (10.62, 21.23, 42.46 g·kg-1), with 10 mice in each group. After 21 days of medication, the content of tumor necrosis factor-α (TNF-α) in serum was detected by enzyme-linked immunosorbent assay (ELISA). The expression of HIF-1α mRNA was detected by real-time fluorogenic quantitative polymerase chain reaction (real-time PCR). Immunohistochemistry (IHC) was employed to detect the expression of HIF-1α, TNF-α, and VEGFA in tumor tissues, and CD34 staining to examine the angiogenesis in tumor tissues. Microvessel density (MVD) was calculated, and the protein expression of HIF-1α, VEGFA, and epidermal growth factor receptor (EGFR) in tumor tissues was measured by Western blot. ResultCompared with the model group, the rest four groups showed low levels of TNF-α (P<0.01), HIF-1α mRNA (P<0.01), expression of HIF-1α, TNF-α, VEGFA, and CD34 in cells, and MVD (P<0.05, P<0.01), and low protein levels of HIF-1α, VEGFA, and EGFR (P<0.01). Compared with capecitabine group, medium-dose and high-dose Chaihu Guizhitang decreased the level of TNF-α (P<0.01), HIF-1α mRNA (P<0.01), expression of HIF-1α, TNF-α, and VEGFA in cells (P<0.01), CD34 expression, MVD, and protein levels of HIF-1α, VEGFA, and EGFR (P<0.01). ConclusionChaihu Guizhitang may inhibit the angiogenesis in TNBC cells by regulating the expression of HIF-1α/VEGFA signaling pathway, thus exerting anti-tumor effect.