Traditional Mongolian medicine RuXian-1 suppress the breast hyperplasia by GRP78/PERK/CHOP pathway in rat model

In this study we aimed to study the protective effect of RuXian-1, which is a traditional Mongolian medicine on hyperplasia of mammary glands in rats and to explore its possible mechanism. Methods: The rat model of breast hyperplasia was induced by intramuscular injection of estradiol benzoate. The rats were randomly divided into 4 groups: saline treatment group (negative control), estrogen treatment group (model group), RuXian-1 treatment group and raloxifene treatment group (positive control). RuXian-1 group and raloxifene group were given 3.0 g/kg of RuXian-1 and 1.8 mg/kg of raloxifene daily for 4 weeks, respectively. After treatment, the breast tissue of each group was harvested and confirmed the expressions levels of glucose-related protein 78 (GRP78), C/EBP homologous protein (CHOP), and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) which were known that functions as an endoplasmic reticulum stress marker by Western blotting. Results: Compared with the normal group, the GRP78, PERK and CHOP protein levels in the breast tissue of the model group were significantly decreased. Compared with the model group, the expression of GRP78, PERK and CHOP in RuXian-1 group significantly increased, the expression of GRP78 and CHOP of raloxifene significantly increased (p < 0.05), and the expression of PERK did not change. Conclusion: The Mongolian medicine RuXian-1 has therapeutic effect on mammary hyperplasia in rats, and its therapeutic mechanism is related to activating the GRP78/PERK/CHOP signaling pathway and promoting mammary gland cell apoptosis.