Expression data from mice bladder with MB49-induced cancer treated with alpha1-oleate.

Potent chemotherapeutic agents are required to counteract the aggressive behavior of cancer cells and patients often experience severe side effects, due to tissue toxicity. This study addresses if a better balance between efficacy and toxicity can be attained using the tumoricidal complex alpha1-oleate, formed by a synthetic, alpha-helical peptide comprising the N-terminal 39 amino acids of alpha-lactalbumin and the fatty acid oleic acid. Bladder cancer was established, by intra-vesical instillation of MB49 cells on day 0 and the treatment group received five instillations of alpha1-oleate (1.7-17mM) on days 3-11. A dose-dependent reduction in tumor size, bladder size and bladder weight was recorded in the alpha1-oleate treated group, compared to sham-treated mice. Tumor markers Ki-67, Cyclin D1 and VEGF were inhibited in a dose-dependent manner, as was the expression of cancer-related genes. Remarkably, toxicity for healthy tissue was not detected in alpha1-oleate-treated, tumor bearing mice or in healthy mice or rabbits, challenged with increasing doses of the active complex. The results define a dose-dependent therapeutic effect of alpha1-oleate in a murine bladder cancer model. Bladder cancer was induced in C57BL/6J female mice by intravesical instillation of MB49 cells. The treatment group received alpha1-oleate by intravesical instillation (1.7 mM, 8.5 mM or 17 mM) on days 3, 5, 7, 9 and 11. Sham treated mice received PBS and healthy mice bladders were used as control. Bladder samples were collected after 12 days. Isolated RNA was subjected to Affymetrix whole genome transcriptomic analysis. For toxicity testing in healthy mice, alpha1-oleate was instilled intravesically in C57BL/6J female mice (17 mM) and bladders were collected for RNA isolation after 24 hours or 7 days. Controls received PBS.