T0070907

Cell lines

MB-231 cells

Preparation Method

Transwell inserts (8μm pore size) were coated with collagen type I. Cells were pre-treated with 0.1, 1, 10, 20μM T0070907 or empty vehicle for 48h, then trypsinized and resuspended in serum-free DMEM containing 1% bovine serum albumin (BSA) to achieve a density of 3×10⁵ cells/mL. Inserts were placed in wells containing normal growth media. A volume of 200μL of cell suspension was added to the upper chamber and incubated at 37˚C with 5% CO₂ for 6h. After incubation, the upper side of membrane was washed and wiped-off using cotton swabs and then cells on the lower membrane surface were fixed with methanol and stained with 0.5% crystal violet. The images of five random fields per well were taken using ×40 objective and the number of migrated cells was counted.

Reaction Conditions

0.1, 1, 10, 20μM; 48h

Applications

T0070907 treatment reduced cell migration in a dose-dependent manner.

Animal models

Male severe combined immunodeficiency (SCID) mice

Preparation Method

Male severe combined immunodeficiency (SCID) mice, 6 weeks of age, were maintained in a specific pathogen-free environment. At day 0, 2×10⁶ HT-29 cells were injected into the spleen. After inoculation, the mice were randomized into 2 treatment groups and 1 control group. Starting at day 1 and daily thereafter, T0070907 (1 or 5mg/kg/day) or control (1% DMSO vehicle) was administered orally. These con centrations were chosen based on initial pilot experiments to detect morbidity based on T0070907 alone. At 1 or 5 mg/kg/day, no increased morbidity (based on grooming, activity and food intake) was noted in mice with or without injected tumor cells. Four weeks later, the number and size of metastatic lesions in the liver were determined.

Dosage form

1, 5mg/kg/day; 4 weeks; p.o.

Applications

Mice treated with 1mg/kg/day of T0070907 orally had half the number of metastatic foci, and the average tumor volume was only 30% of that seen with control mice. A small increase in efficacy was seen when the dose of drug was increased to 5mg/kg/day.

References:
[1] Zaytseva Y Y, Wallis N K, Southard R C, et al. The PPARγ antagonist T0070907 suppresses breast cancer cell proliferation and motility via both PPARγ-dependent and-independent mechanisms[J]. Anticancer research, 2011, 31(3): 813-823.
[2]Schaefer K L, Takahashi H, Morales V M, et al. PPARγ inhibitors reduce tubulin protein levels by a PPARγ, PPARδ and proteasome?independent mechanism, resulting in cell cycle arrest, apoptosis and reduced metastasis of colorectal carcinoma cells[J]. International journal of cancer, 2007, 120(3): 702-713.