A novel anti-adhesion peptide (β3) inhibits hepatocellular carcinoma activity in vitro and in vivo.

The present study aimed to investigate the blocking of tumor cell adhesion to the extracellular matrix, the prevention of tumor metastasis by the β peptide trimer β3, as well as the influence of β3 on the recurrence and survival time of hepatocellular carcinoma (HCC) nude mice model LCI-D20 after early resection. To this end, the DNA fragment of the β3 peptide (DLYYLMDLSYSMKGGDLYYLMDLSYSMKGGDLYYLMDLSYSMK) 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 HCC cell line HCCLM6 to fibronectin (FN) was measured by 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 HCC and mouse survival time after early resection was investigated using the HCC metastasis nude mice model LCI-D20. HCCLM6 cells incubated with 10, 20, 50 or 100 µmol/l β3 for 3 h demonstrated a marked reduction in adhesion to FN. The adhesion inhibition rates were 11.8, 21.7, 37.5 and 66.4%, respectively. In addition, cell invasion was reduced by 51.3% in HCCLM6 cells cultured with 100 µmol/l β3. Treatment with β3 also inhibited tumor recurrence at the incisal edge and prolonged the survival time of LCI-D20 mice following early resection. The present study provided evidence that β3 peptide specifically blocked the adhesion and invasion of HCCLM6 cells, inhibited HCC recurrence in vivo and prolonged the survival time of HCC nude mice LCI-D20 following hepatectomy. Therefore, β3 may be further investigated as a novel anti-tumor drug.