Anti-tumor effects of a novel chimeric peptide on S180 and H22 xenografts bearing nude mice.
In recent years, many endogenous peptides have been identified by screening combinatory phage display peptide library, which play important roles in the process of angiogenesis. A heptapeptide, ATWLPPR, binds specifically to NRP-1 and selectively inhibits VEGF165 binding to VEGFR-2. Another heptapeptide, NLLMAAS, blocks both Ang-1 and Ang-2 binding to Tie-2 in a dose-dependent manner. In the present study, we aimed to connect ATWLPPR (V1) with NLLMAAS (V2) via a flexible linker, Ala-Ala, to reconstruct a novel peptide ATWLPPRAANLLMAAS (V3). We firstly investigated the anti-tumor and anti-angiogenic effects of peptide V3 on sarcoma S180 and hepatoma H22 bearing BALB/c nude mice. Mice were continuously subcutaneously administrated with normal saline, V1 (320microg/kg/d), V2 (320microg/kg/d), V1+V2 (320microg/kg/d), and V3 (160, 320 and 480microg/kg/d), for 7 days. Treatment with peptide V3 could significantly reduce the tumor weight and volume. Pathological examination showed that the tumors treated with peptide V3 had a larger region of necrosis than that of peptide V1, V2, and V1+V2 at the same dose. A significant decrease of microvessel density (MVD) in a dose-dependent manner was observed in each group of peptide V3. The results of pathological examination on normal tissue, lung, heart, liver, spleen, kidney and white blood cells showed that peptide V3 might have no significant toxicity. In conclusion, our results demonstrated that peptide V3 could be more effective on inhibiting tumor growth and angiogenesis than that of V1, V2, and V1+V2. Peptide V3 could be considered as a novel chimeric peptide with potent anti-tumor activity.
Department of Bioengineering, Zhengzhou University, Science Road 100, Zhengzhou 450001, China.
Dongdong
D
Wu
Yanfeng
Y
Gao
Lixiang
L
Chen
Yuanming
Y
Qi
Qiaozhen
Q
Kang
Haili
H
Wang
Linyu
L
Zhu
Yong
Y
Ye
Mingxia
M
Zhai
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D011897:Random Allocation; D023041:Xenograft Model Antitumor Assays
D018952:Antigens, CD34; D010455:Peptides