Combretastatin A-1 is a potent microtubule inhibitor with anti-tumour and anti-vascular activity, acting through microtubule protein depolymerisation-mediated inactivation of AKT to inhibit the Wnt/β-catenin pathway, and can be used to study hepatocellular carcinoma.

CT-26:1075 nM, Hepa 1-6:32.9 nM, HepG2 cells:9.2 nM, Huh7:728.2 nM, A375:61 nM, LM-3:33.8 nM, Bel-7402:38.4 nM, MCF-7 cells:46.0 nM, Smmc 7721 cells:12.8 nM, NCI-1975:256.3 nM, BGC-803:12.2 nM, MDA-MB-231 cells:17.6 nM

Combretastatin A-1 (CA1P) induces apoptosis of TAMs in vitro through the same mechanism observed in HepG2 cells, and it eliminates TAMs in the tumor microenvironment (TME) in vivo. Combretastatin A-1 (1-10 nM; 24 hours) induces AKT inactivation and removal of GSK-3β inhibition by microtubule depolymerization, leading to HepG2 cell apoptosis [2]. Combretastatin A-1 (1-50 nM; 6 hours) reduces the mitochondrial membrane potential (MMP) of HepG2 cells and induces the accumulation of ROS in a dose-dependent manner [3].

In the HepG2 subcutaneous xenograft model, Combretastatin A-1 (1-4 mg/kg; i.v. every other day for 4 weeks) significantly reduces the tumor volume [3].
In the orthotopic hepatocellular carcinoma mouse model, Combretastatin A-1 (2 mg/kg; every other day for 21 days) demonstrates enhanced apoptosis [3].