Fig. 4.

The potent anti-tumor activity of PA-L1/LF is not solely dependent on its inhibitory effects on IL8.

(A) Angiogenic factor profiling RT-PCR analysis reveals that the expression of IL8 by tumor cells is down-regulated by anthrax lethal toxin. Colo205, A549/ATCC, HT144, and HT29 cells were treated with or without PA/LF (10/3.3 nM) for 8 h, then the total RNA was isolated, and subjected to the angiogenic factor RT-PCR profiling analyses following the recommendations of the manufacturer. Note that IL8 is consistently down-regulated by PA/LF in all four cancer cell lines. ANGP1, angiopoietin 1; CSF3, colony stimulating factor 3; ECGF1, endothelial cell growth factor 1; FGF1 and FGF2, fibroblast growth factor 1 and 2; FST, follistatin; HGF, hepatocyte growth factor; LEP, leptin; PDGFB, platelet derived growth factor B; PGF, placental growth factor.

(B-C) Both A549/ATCC carcinomas (B) and C32 melanomas (C) transfected with lethal LT ‘resistant’ IL8 retain susceptibility to PA-L1/LF. Nude mice bearing tumors transfected with IL8 or the empty vector were treated with 6 doses of 30/10 μg of PA-L1/LF or PBS. PA- L1/LF shows potent anti-tumor activity against the tumors transfected with either IL8 or the empty vector.