A cyclic peptide antagonist of N-cadherin
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ADH-1 is a cyclic peptide antagonist of N-cadherin. 1 It inhibits neurite outgrowth in cerebellar neurons cultured on N-cadherin-expressing 3T3 cell monolayers (IC50 = 0.323 mM). ADH-1 (0.2 mg/ml) inhibits cell scattering and motility induced by collagen I in Capan-1 cells and wild-type and N-cadherin-overexpressing BxPC-3 cells.2 It induces apoptosis in N-cadherin-overexpressing, but not knockdown, BxPC-3 cells when used at a concentration of 1 mg/ml. ADH-1 (50 mg/kg) reduces tumor growth in an N-cadherin-overexpressing BxPC-3 mouse xenograft model.
1.Williams, E., Williams, G., Gour, B.J., et al.A novel family of cyclic peptide antagonists suggests that N-cadherin specificity is determined by amino acids that flank the HAV motifJ. Biol. Chem.275(6)4007-4012(2000) 2.Shintani, Y., Fukumoto, Y., Chaika, N., et al.ADH-1 suppresses N-cadherin-dependent pancreatic cancer progressionInt. J. Cancer122(1)71-77(2008)
Animal experiment: | Animals are anesthetized, and 40 μL of a single cell suspension containing 50,000 cells is injected into the pancreas. Mice are randomized into treatment groups 10 days after surgery. For treatment, mice are injected intraperitoneally once per day with ADH-1 at 50 mg/kg in 100 μL PBS (×1 per day, ×5 per week for 4 weeks). For in vivo bioluminescence, D-Luciferin is administered by intraperitoneal injection. Data are acquired 20 min after injection using the IVIS system. Tumor growth is monitored every 10 days from day 10 to day 50 after surgery. Luciferase activity is quantified using the IVIS system. Two months after surgery, the mice are killed, and the pancreas, liver, lung, and disseminated nodules are harvested, fixed in 10% buffered formalin, and embedded in paraffin. Serial 5-μM sections are cut, mounted on slides, and stained with H&E using standard procedures. Sections are also stained for TUNEL. Sections are examined using a Zeiss Axioscop 40 microscope equipped with an AxioCam MR digital camera and software. |
参考文献: [1]. Shintani Y, et al. ADH-1 suppresses N-cadherin-dependent pancreatic cancer progression. Int J Cancer. 2008 Jan 1;122(1):71-7. |
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