Diwu Yanggan capcules alleviate hepatocellular carcinoma progression by regulating YAP signaling
Hepatocellular carcinoma (HCC) is a highly malignant tumor with poor prognosis, and its progression typically follows a stepwise pathological process of "hepatitis-liver fibrosis-cirrhosis-HCC." Due to the complex pathogenesis and prolonged disease course, effective early intervention strategies remain limited, highlighting the critical need for novel preventive and therapeutic approaches.In our previous study, the Chinese herbal compound DWYG was found to significantly ameliorate liver fibrosis and reduce the incidence of cirrhosis. Given that fibrosis and cirrhosis are well-established risk factors for HCC development, we hypothesize that DWYG may exert preventive effects against HCC by interrupting this pathological progression.To test this hypothesis, we will establish a DEN/CCl4-induced primary HCC mouse model to systematically evaluate the interventional effects of DWYG on hepatocarcinogenesis. Furthermore, RNA sequencing (RNA-seq) and molecular biology techniques will be employed to elucidate the underlying mechanisms. Overall design: Twenty-four 2-week-old male C57BL/6 mice were randomly divided into four groups (n=6 per group): one control group and three HCC model groups. The model groups received intraperitoneal (i.p.) injections of diethylnitrosamine (DEN, 0.67% v/w), while the control group received equivalent volumes of normal saline. Starting at 8 weeks of age, the model groups were administered carbon tetrachloride (CCl4, 20% in olive oil, i.p.) twice weekly until the end of the experiment. At 17 weeks of age, two model groups began receiving DWYG treatment: one group received the clinical equivalent dose (medium-dose group, DWYG-M) and the other received twice the clinical equivalent dose (high-dose group, DWYG-H). All mice were sacrificed at 22 weeks of age for liver tissue collection. From each group, two randomly selected liver samples were subjected to RNA sequencing (RNA-seq) to analyze differentially expressed genes and investigate underlying molecular mechanisms.