Inhibitory effect and its mechanism of guggulsterone on diethylnitrosamine-induced hepatocellular carcinoma in rats

Abstract

Abstract: Objective To explore the inhibitory effect and its mechanism.of guggulsterone (GS) on diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats. Methods DEN-induced HCC model was constructed in SD rats. Successful HCC modeling rats were randomly divided into the HCC group (n=6) and the GS group (n=6, 50 mg/kg), and free-feeding rats were randomly selected as the control group (n=6). The GS group was continuously injected with GS for four weeks, while the control group and HCC group were injected with an equal amount of physiological saline. The liver gross morphology was observed and the body mass, liver mass and liver-body mass ratio were measured in rats. Pathological changes of rat liver were detected by hematoxylin and eosin (HE) Staining staining, and the expression levels of p53-associated mitochondrial apoptotic signaling pathway proteins, p53, B-cell lymphoma 2 (Bcl-2), BCL2-associated X protein (Bax), caspase-3, and caspase-9 were detected by immunohistochemistry staining and Western blot methods, respectively. Results Compared with the control group (501.04 ± 18.03) g, the body mass of rats was significantly decreased in both HCC (406.07 ± 22.91) g and GS groups [(357.83 ± 29.01)g, P<0.001]. The liver mass and liver body mass ratio of the HCC group (27.68 ± 6.34, 6.88 ± 1.87) g and the GS group (18.25 ± 2.20, 5.13 ± 0.72) g were significantly higher than those of control group (13.67 ± 1.40, 2.74 ± 0.38) g, and the GS group was lower than the HCC group (P=0.002, P=0.003). The liver of the HCC group was enlarged with multiple cancerous nodules diffusely distributed on the surface, and multiple cancerous nodules diffusely distributed were also seen in the GS group, but the number of cancerous nodules was significantly reduced compared with that in the HCC group. Microscopically, the phenomena of hepatocellular heterogeneous hyperplasia and focal nodular hyperplasia were seen in the HCC group, whereas hepatocellular heterogeneous hyperplasia necrosis and focal nodular hyperplasia were significantly improved in the GS group. Immunohistochemistry showed that the protein expression levels of p53 (56.42 ± 6.84), Bax (43.02 ± 5.27) and caspase-3 (13.37 ± 2.50) in the GS group were significantly higher than those in the control group (19.33 ± 2.98, 16.07 ± 3.22, 3.42 ± 1.04) and the HCC group (39.32 ± 5.99, 27.42 ± 3.74, 9.63 ± 1.53), and there was a statistically significant difference in the comparison of the three groups (P<0.05), while the protein expression level of Bcl-2 (8.52 ± 3.31) was significantly lower than that in the control group (22.03 ± 3.74) and the HCC group (15.38 ± 2.10), and there was a statistically significant difference among the comparison of the three groups (P<0.05). The caspase-9 protein expression level was not statistically different among the three groups (1.27 ± 0.71, 1.07 ± 0.70, 1.43 ± 0.81, P>0.05). Similar results were obtained by Western blot. Conclusion GS inhibited DEN-induced HCC, which may be related to the p53-related mitochondrial apoptotic signaling pathway.

Key words: Guggulsterone, Hepatocellular carcinoma, P53, Diethylnitrosamine

LIU Xiong-tao, WANG Yi-kai, XUE Peng-jun, KANG Pei, ZHANG Xin, SHI Juan-juan. Inhibitory effect and its mechanism of guggulsterone on diethylnitrosamine-induced hepatocellular carcinoma in rats[J]. Chinese Hepatolgy, 2025, 30(9): 1225-1229.

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