Abstract: Objective: To investigate the effects and mechanisms of Periplaneta americana peptides PAP-2 on the angiogenesis,
invasion and metastasis of hepatocellular carcinoma by in vivo experiments. Methods: Establish a tumor-bearing model of Balb/c mice
and observe the effects of Periplaneta americana peptides PAP-2, CⅡ-3 and skimmed cream on tumor growth ability. Hematoxylineosin（
HE）staining was used to observe the pathological changes of tumor tissue. Enzyme linked immunosorbent assay（ELISA）and
immunohistochemical staining（IHC）methods were used to determine serum levels of basic fibroblast growth factor（bFGF）, CD34
molecule, metal matrix proteinase-9（MMP-9）and transforming growth factor-β（TGF-β）in mice serum, and the expression level of
the corresponding protein in the tumor tissue. Real-time quantitative polymerase chain reaction（Real-time qPCR） was used to
determine the mRNA expression levels of bFGF, MMP-9 and TGF-β in tumor tissues. Results: PAP-2 can inhibit the growth of
tumors and increase the organ index of mice. HE staining of H22 tumor-bearing mice showed necrosis in different dose groups. PAP-2
can down-regulate the bFGF content in the serum of mice; PAP-2 can down-regulates the expression of bFGF, CD34, MMP-9 and
TGF-β proteins in tumor tissues better than C Ⅱ -3 and skimmed cream（P < 0.05）. Different doses of PAP-2 can promote the
expression of MMP-9 mRNA, bFGF mRNA, and TGF-β mRNA in tumor tissues. Conclusion: PAP-2 can inhibit the tumor growth of
H22 tumor-bearing mice, and its mechanism is related to the down-regulation of bFGF, CD34, MMP-9 and TGF-β protein expression
in hepatocarcinoma tissues, PAP-2 has a better effect than CⅡ-3 and skimmed cream.

Key words: angiogenesis, hepatocellular carcinoma, invasiveness, metastasis, Periplaneta americana polypeptide