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Effects of Bushen Jianpi formula on farnesoid X receptor-mediated inhibition of hepatocellular carcinoma AH-130 cell-induced cachexia in rats and its underlying mechanism
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Abstract:
[Abstract] Objective: To investigate the effects of Bushen Jianpi formula (BSJP) in mediating the inhibitory effects of farnesoid X receptor (FXR) on cancer cachexia (CC) induced by hepatocellular carcinoma AH-130 cells in a rat model and its underlying mechanism. Methods: A liver cancer cachexia rat model was established by intraperitoneal injection of AH-130 cells. The rats were divided into five groups: blank control, model control, CDCA (FXR agonist), BSJP, and BSJP + CDCA groups. After modelling, the rats were treated with CDCA, BSJP, or their combination for consecutive 16 days, and their body weights were measured weekly. At the end of the experiment, the rats were sacrificed, and abdominal aortic blood, feces, and brown adipose tissues from the epididymal, inguinal, and scapular regions were collected. Liquid chromatography-mass spectrometry (LC-MS) was used to detect the composition and content of bile acids in serum and feces of rats. WB and qPCR were used to detect the expression of FXR, Wnt family member 10b (Wnt10b), β -catenin, and uncoupling protein 1 (UCP-1) in the ileum, brown adipose, and white adipose tissues of rats. Results: Compared with the blank control group, the body mass of the rats in the model group was significantly reduced (P < 0.01); compared with the model control group, the body mass of the rats in CDCA, BSJP and BSJP + CDCA groups all increased (P < 0.01). Compared with the blank control group, the epididymal, inguinal, scapular, and total brown adipose tissue mass were all elevated in the model control group (all P < 0.05); compared with the model control group, the brown fat mass in the inguinal and epididymis regions of the rats decreased significantly in all treatment groups (P < 0.05), but this decrease was not significant in the scapular region (P > 0.05); besides, the total brown fat mass decreased notably in all treatment groups compared to the model control group (all P < 0.01). LC-MS analysis showed that the composition and content of bile acids in the serum and feces of rats were altered in all groups. qPCR and WB results confirmed that, compared to the model group, BSJP and BSJP + CDCA promoted the mRNA and protein expression of FXR in the ileum, brown adipose, and white adipose tissues of rats (all P < 0.05), and decreased the mRNA and protein expression of Wnt10b, β-catenin, UCP-1 (all P < 0.05). Conclusion: The BSJP formula can inhibit hepatocellular carcinoma cell AH-130-induced cachexia in rats, alleviating the associated body weight loss and brown adipose tissue formation. The mechanism may involve the regulation of FXR and the inhibition of the expression of Wnt10b, β -catenin, and UCP-1 in brown adipose tissue through the Wnt signaling pathway.
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