Certepetide

Cell lines

GFP-PC-3 cells; LM-PmC cells

Preparation Method

Cell migration was analyzed using 24-well Transwell chambers containing polycarbonate membranes with 8-μm pores. Both sides of the membranes were coated with 50μg/ml of collagen type-I to facilitate initial cell attachment to the membranes. GFP-PC-3 (4 × 10⁴ cells) or LM-PmC (2 × 10⁵ cells) cells in DMEM containing 0.1% BSA were added to the upper compartment. The lower compartment was filled with 600μl of DMEM containing 0.1% BSA. Certepetide at a final concentration of 10μM or PBS were added to both the upper and lower compartments. The total number of cells that migrated to the lower side of the membranes was determined by counting cell numbers under low magnification.

Reaction Conditions

10μM; 24h

Applications

Certepetide can inhibit the in vitro random migration ability of LM-PmC and GFP-PC-3 tumor cells, which is helpful in preventing the initial metastasis of tumor cells.

Animal models

Nude mice

Preparation Method

A total of 5 × 10⁶ HepG2 or Huh-7 cells (resuspended in 100μL of PBS) was injected subcutaneously into nude mice. Three to 4 weeks later, the mice were assigned to the treatment groups. Doxorubicin was dissolved in PBS and sorafenib in a vehicle containing 12.5% Cremophor and 12.5% ethanol. Nude mice bearing HepG2 or Huh-7 xenografts received Certepetide (4μmol/kg by tail vein injection), or PBS 15 minutes each time before treatment with doxorubicin (3mg/kg, 3 times per week intraperitoneally) or sorafenib (every second day orally). Body weight and tumor size were determined every 2 to 3 days with a caliper. At the end of the experiment, the mice were sacrificed by cervical dislocation. Tumors were excised and weighed.

Dosage form

4μmol/kg; 28 days; i.v.

Applications

Certepetide can increase the concentration of sorafenib in subcutaneous tumor tissues without increasing systemic toxic effects and enhancing the killing ability of toxic T cells

References:
[1]Sugahara KN, Teesalu T, Karmali PP, Kotamraju VR, Agemy L, Girard OM, Hanahan D, Mattrey RF, Ruoslahti E. Tissue-penetrating delivery of compounds and nanoparticles into tumors. Cancer Cell. 2009 Dec 8;16(6):510-20.
[2]Schmithals C, Köberle V, Korkusuz H, Pleli T, Kakoschky B, Augusto EA, Ibrahim AA, Arencibia JM, Vafaizadeh V, Groner B, Korf HW, Kronenberger B, Zeuzem S, Vogl TJ, Waidmann O, Piiper A. Improving Drug Penetrability with iRGD Leverages the Therapeutic Response to Sorafenib and Doxorubicin in Hepatocellular Carcinoma. Cancer Res. 2015 Aug 1;75(15):3147-54.