Purpose: 1) To investigate the blocking of tumor cell adhesion to the extracellular matrix,and the prevention of tumor metastasis by the β peptide trimer β3.2) To study the influence of β3 on the recurrence of mouse hepatocellular carcinoma and mouse survival time after early resection.METHODS: The DNA fragment of β3 peptide (DLYYLMDLSYSMKCrGDLYYLMDLSYSMK GGDLYYLMDLSYSMK) was cloned into the expression vector pET-His and the fusion protein His-β3 was expressed in E.coli BL21(DE3)plysS.The anti-adhesion effect of β3 on the highly metastatic hepatocellular carcinoma (HCC) cell line HCCLM6 to fibronectin (FN) was assayed by the MTT assay.The inhibition of HCCLM6 cell invasion by β3 was analyzed using a Transwell (modified Boyden chamber) system and matrigel.The influence of β3 on the recurrence of hepatocellular carcinoma and mouse survival time after early resection was investigated using the hepatocellular carcinoma metastasis nude mice model LCI-D20.RESULTS: HCCLM6 cells incubated with 10 μmol/L,20 μmol/L,50 μmol/L or 100 μnol/L β3 for 3 h showed an obvious decrease in adhesion to FN.The adhesion inhibition rates were 11.8 %,21.7 %,37.5 %,and 66.4 %,respectively.Additionally,HCCLM6 cells cultured with 100 μmol/L β3 had a dramatic decrease in cell invasion with an inhibition rate of 51.3 %.β3 also inhibited the incisal edge tumor recurrence and prolonged the survival time of LCI-D20 mice after early resection.CONCLUSIONS: The β3 peptide can specifically block the adhesion and invasion of HCCLM6 cells,inhibit HCC recurrence in vivo and prolong the survival time of hepatocellular carcinoma nude mice LCI-D20 posthepatectomy.Thus,β3 could be further explored as a new anti-tumor drug.