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iMDK is a suppressor of endogenous midkine (MDK) expression. Inhibits PI 3-K signaling in H441 lung adenocarcinoma cells. Selectively attenuates growth of MDK-expressing cancer cells.
Intraperitoneally injected with 100 μL (9 mg/kg) iMDK everyday and/or orally administered PD0325901 five times per week (on days 1, 2, 3, 4, 5, 7, 8, 9, 10, 11) significantly reduced the volume of the tumors in a female BALB/c nude mice (6 week old) bearing H441 human lung cancer xenografts model.
Mouse experiments
Human lung cancer xenografts were established in 6-wk-old female BALB/c nude mice (Charles River Laboratories Japan, Kanagawa, Japan) by subcutaneous (s.c.) inoculation of H441 cells (1 × 106/50 μl) into the right dorsal flank. The mice were randomly assigned into four groups (n=8 per group) 9 days after tumor inoculations. The mice were intraperitoneally injected with 100 μl solution containing iMDK (9 mg/kg) everyday and/or orally administered PD0325901 (5 mg/kg) in 0.5% [w/v] methylcellulose solution with 0.2% [v/v] polysorbate 80 [Tween 80] five times per week (on days 1, 2, 3, 4, 5, 7, 8, 9, 10, 11). DMSO was intraperitoneally injected and methylcellulose solution with polysorbate 80 was orally administered in the control group. Tumors were measured every day, and tumor volume was calculated as a × b2 × 0.5, where a and b were large and small diameters, respectively. On day 11, all mice were sacrificed and tumors were removed and prepared for histology.
| Cell Experiment | |
|---|---|
| Cell lines | H441 cells, H2009 cells, H520 cells and A549 cells |
| Preparation method | Cell viability assay H441 cells and H2009 cells were plated in 96-well plates at a density of 1.5 × 10^3 cells and cultured at 37 °C for 24 h. H441 and H2009 cells were treated with or without iMDK (2.5 μM) in the presence or absence of PD0325901 (0.5 μM). H520 cells were treated with or without iMDK (0.125 μM) in the presence or absence of PD0325901 (0.25 μM). A549 cells were treated with or without iMDK (0.25 μM) in the presence or absence of PD0325901 (0.125 μM). Cells were treated for 72 h. Viable cells were assessed by WST-1 assays. |
| Concentrations | 2.5 μM, 0.125 μM, 0.25 μM |
| Incubation time | 72 h |
| Animal Experiment | |
|---|---|
| Animal models | female BALB/c nude mice (6 week old) bearing H441 human lung cancer xenografts |
| Formulation | DMSO |
| Dosages | 100 μl (9 mg/kg/day) |
| Administration | intraperitoneally injected |
| Molecular Weight | 376.4 |
| Formula | C21H13FN2O2S |
| CAS Number | 881970-80-5 |
| Solubility (25°C) | DMSO 1.88 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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