Cell lines

PLC/PRF/5 cells

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20 μM, 72 hours for migration assay 5 μM, 24 hours for invasion assay

Applications

For the migration assay, PLC/PRF/5 cells were treated with the drugs and microscopically analyzed at the time of the scratch (T0) and after 48 and 72 hours. For the invasion assay, invading PLC/PRF/5 cells were treated with different drug concentrations (0.5, 1, 2.5 and 5 μM). Invasion was calculated as a percentage of the invading drug-treated cells compared to drug-untreated control cells. Regorafenib inhibited HCC cell migration in both AFP-positive and AFP-negative cells at the same low concentration range as inhibited AFP levels. Similar results were found in a cell invasion assay, at almost identical drug concentrations.

Animal models

Female athymic NCr nu/nu mice injected with Colo-205, MDA-MB-231 or 786-O xenografts

Dosage form

Oral administration; 100, 30, 10, and 3 mg/kg

Applications

Regorafenib dosed qd orally inhibited tumor growth in a dose-dependent manner in multiple xenograft models, including models derived from CRC (Colo-205), BC (MDA-MB-231) and RCC (786-O) tumors. Regorafenib effectively inhibited growth of the Colo-205 xenografts in the dose range of 10-100 mg/kg, reaching a TGI of about 75% at day 14 at the 10 mg/kg dose. A slow regrowth was observed at all doses when treatment was terminated after 9 days. In the MDA-MB-231 model, regorafenib was highly efficacious at a dose as low as 3 mg/kg, resulting in a significant TGI of 81%, which increased to ~ 93% at doses of 10 and 30 mg/kg, where tumor stasis was reached. Regorafenib also very efficiently inhibited the growth of the 786-O RCC model. TGI >90% was observed at the end of a 21-day dosing period with regorafenib 10 and 30 mg/kg.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1] Carr B I, D'Alessandro R, Refolo M G, et al. Effects of low concentrations of regorafenib and sorafenib on human HCC cell AFP, migration, invasion, and growth in vitro. Journal of cellular physiology, 2013, 228(6): 1344-1350.

[2] Wilhelm S M, Dumas J, Adnane L, et al. Regorafenib (BAY 73): A new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. International Journal of Cancer, 2011, 129(1): 245-255.