| Objective? To explore the mechanism by which Babao Dan prevents and treats endocrine therapy-related dyslipidemia in breast cancer, based on the Liver X Receptor alpha (LXRα) signaling pathway. Methods? After one week of adaptive feeding, 30 mice were randomly divided into two groups: 6 mice served as the blank control group without any intervention, and the remaining 24 mice were assigned to the VCD inhibition group, which received intraperitoneal injection of VCD at 160 mg/kg/day for 16 consecutive days. From the VCD inhibition group, 18 nude mice with similar body weight and good physical condition were selected to establish a human breast cancer MCF-7 cell xenograft model, and the success of modeling was verified by ELISA and Wright"s staining. Subsequently, the 18 successfully modeled nude mice were randomly divided into three groups with 6 mice each: the model group, the endocrine group, and the combination group.The intervention protocols for each group were specified as follows: the blank control group received no intervention throughout the experiment, serving as the reference for baseline blood lipid levels; the model group was not administered any additional drugs after modeling; the endocrine group was intraperitoneally injected with letrozole (an endocrine therapy drug) at 1 mg/kg/day for 3 consecutive weeks, and dyslipidemia occurred after this endocrine therapy; the combination group was given intragastric gavage of Babao Dan solution at 125 mg/kg/day, while receiving intraperitoneal injection of letrozole at 1 mg/kg/day for 3 consecutive weeks.After 3 weeks of drug intervention, the tumors of nude mice were harvested. Tumor weight and volume were measured to calculate the tumor growth inhibition rate. Biochemical assays were conducted to determine the serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Hematoxylin-eosin (HE) staining was applied to observe the morphology, structure, and number of lipid vacuoles in liver tissue. The thiobarbituric acid (TBA) method was used to detect malondialdehyde (MDA) content, and the hydroxylamine method was adopted to measure superoxide dismutase (SOD) activity. ELISA was used to detect the contents of inflammatory cytokines TNF-α and IL-6 in liver tissue, and immunohistochemistry (IHC) was employed to examine the protein expressions of LXRα, ABCA1, ABCG5, and CYP7A1 in liver tissue. Results Compared with the endocrine group, the combination group showed a more significant inhibitory effect on tumor cell growth in mice (P<0.05), with a tumor inhibition rate of 82.49%. Meanwhile, the combination group had significantly lower serum levels of ALT, TC, LDL-C, AST, and TG, and a significantly higher serum HDL-C level (P<0.05). Pathological damage to liver tissue in the combination group was significantly alleviated compared with that in the endocrine group. In addition, the combination group exhibited increased serum SOD content and decreased MDA content (P<0.05), as well as significantly lower serum levels of TNF-α and IL-6 (P<0.05) and significantly enhanced expressions of LXRα-related proteins (P<0.05) compared with the endocrine group. Conclusion Babao Dan can prevent and treat endocrine therapy-related dyslipidemia in breast cancer by promoting the expressions of LXRα-mediated signaling molecules ABCA1, ABCG5, and CYP7A1, thereby facilitating cholesterol efflux and conversion, reducing inflammatory response, and improving antioxidant stress capacity. |