To establish a mouse model of hepatocellular carcinoma (HCC) with vessels encapsulating tumor clusters (VETC) and to evaluate the effect of sorafenib on VETC(+) HCC.

49 C57 mice were randomly divided into the prevention (n=15), treatment (n=15) and control groups (n=19). In the prevention group, HEP1-6 HCC cells were inoculated under the liver capsule with a dosage of 5×10⁵ cells per mouse, and after 2 d, sorafenib solution was continuously administered by gavage (25 mg/kg, once daily). In the treatment group, sorafenib solution was continuously given by gavage (50 mg/kg, once daily) at 10 d after inoculation. In the control group, an equivalent amount of DMSO was given by gavage. Mice were sacrificed at 5, 10, 15, 20, 23 and 27 d after inoculation, respectively. The tumor tissues were embedded in paraffin and sliced up for CD34 and HE staining. The weight and adverse reactions of mice were observed. The tumor formation and maximum tumor diameter were recorded. The maximum tumor diameter and number of VETC rings were compared by Kruskal-Wallis test.

All the mice in the groups successfully developed tumors. At 20 d after inoculation, 2 mice had intraheptic metastatic lesions in the control group, and 1 mouse died of tumor progression at 23 d after inoculation. No evident intrahepatic metastasis was observed in the treatment and prevention groups. Desquamation was observed in the mice. No obvious adverse reactions, such as anorexia and diarrhea, were seen. No significant change in weight was noted. The mouse cage was dry and no mouse died. In the prevention group, the maximum tumor diameter was significantly smaller than those in the control group at 5, 10, 15, 20 and 23 d after inoculation (H=-4.355, -3.857, -6.000, -6.250, -6.167; P<0.05). At 15 d after inoculation, the maximum tumor diameter in the treatment group was significantly smaller than that in the control group (H=-5.125, P<0.05). At 5 d after inoculation, evident VETC structure could be observed in mouse liver tumors in the control group. At 15 d after inoculation, the number of VETC rings was significantly lower compared with that at 5 d (H=-3.857, P<0.05), and a large quantity of necrotic foci were observed in the tumors. At 23 d after inoculation, the number of VETC rings was significantly larger than that at 15 d (H=4.582, P<0.05). In the prevention group, the formation of VETC was significantly inhibited at 5-23 d after inoculation, the number of VETC rings at 5, 10 and 20 d was significantly less than those in the control group (H=-3.971, -4.355, -6.369; P<0.05).

The mouse model of VETC(+) HCC is successfully established in this study. Sorafenib can effectively reduce the tumor load, destroy the VETC structure and suppress the formation of VETC in HCC mouse models, especially in the prevention group.