External use of Ruyanneixiao cream efficiently blocks precancerous mammary lesions by interfering with glycolysis induced by inhibition of hypoxia inducible factor-1α, hexokinase 2, phosphofructokinase, and pyruvate kinase M2 expression

Abstract Objective To investigate the effect of Ruyanneixiao cream (RYNX) on the expression of hypoxia inducible factor-1α (HIF-1α), hexokinase 2 (HK2), phosphofructokinase (PFK), and pyruvate kinase M2 (PKM2) mRNA and protein in MCF-10AT cells and in an animal model of precancerous mammary lesions. Methods Following treatment of MCF-10AT cells with RYNX, tamoxifen (TAM) and YC-1 for 48 h, HIF-1α, HK2, PFK, PKM2 mRNA and protein expression was analyzed. Fifty female SD rats were randomly divided into control, model, TAM, and high- and low-dose RYNX groups, with 10 rats in each group. A precancerous mammary lesion model was established for all groups except the control group. High- and low-dose RYNX cream containing TAM was coated on the breasts of animals in the corresponding groups. The rat mammary tissue was removed in the 10th week and HIF-1α, HK2, PFK, PKM2 mRNA and protein was analyzed. Results In vitro analyses demonstrated that, compared with the matrix group, HIF-1α, HK2, PFK, PKM2 mRNA and protein expression was significantly decreased in the RYNX group (P Conclusion RYNX can block precancerous breast lesions by decreasing the expression of HK2, PFK, and PKM2 mRNA and protein via inhibition of HIF-1α mRNA and protein overexpression in a dose-dependent manner.