To explore the inhibitory effect of lenvatinib on the growth of hepatocellular carcinoma (HCC) in a nude mouse model bearing HepG2 cell xenograft and its regulation on the circadian clock gene expression in HCC tissues.

HepG2 cells were inoculated intradermally intothe nude mice to establish xenograft models. After tumorigenesis, all of the mice were randomlydivided into two groups including the observation group and the control group, which were given lenvatinib 30 mg·kg^-1·d^-1, once a day and DMSO 100 μl·20 g^-1·d^-1, once a day for 14 days by intragastric administration, respectively. During the experiment, the tumor volume was measured every 3 days to draw the growth curve of transplanted tumor. The nude mice were killed after 2 weeks and the tumor bodies were stripped. The volume and weight of the tumor were compared between the two groups. The expression levels of circadian clock genes (BMAL1, CKIε, PER1, PER2, PER3, CRY1, CRY2, CLOCK, NPAS2, REV-Erbα, TIM and DEC2) were detected by the Real-time polymerase chain reaction ( Real-time PCR).

Compared with the control group, the nude mice treated with lenvatinib were generally in good condition and the transplanted tumor grew more slowly and the volume was smaller; and after 9 days of administration, the growth slowed down significantly (P<0.05). And the final tumor mass was(0.235±0.43) g, which was significantly lower than that in the control group (0.633±0.22) g (P=0.006, 95%CI=0.167-0.629). The body mass of both groups increased with time. On the 9th day after intragastric administration, the body mass of the treated group was larger than that of the control group (F=5.194, P=0.034). Compared with the control group, the expression levels of BMAL1, CKIε, PER3 and NPAS2 genes increased, DEC2, PER1, PER2 and CRY2 decreased in the observation group, and the differences were statistically significant (all P<0.05). However, there were no significant differences in CLOCK, CRY1, REV-Erbα and TIM.

Lenvatinib inhibits the growth of HCC in nude mice, which can up-regulate the expression of BMAL1, CKIε, PER3 and NPAS2 genes, at the same time, down-regulate the expression of DEC2, PER1, PER2 and CRY2 genes in nude mice.