Figure 8. Valproate pre-treatment of AR-BT474 cells growing in mouse brains enhances animal survival. (A) Intracerebral injection of WT-BT474 and AR-BT474 cells was performed over 10 min (1 × 10⁶ cells, each). Seven days after tumor cell implantation, animals were segregated into treatment groups. For animal administration sodium valproate was dissolved in saline. Animals were treated with saline vehicle or sodium valproate to a final concentration of 100 mg/kg QD for 2 d. For animal administration, lapatinib and obatoclax were first dissolved in DMSO, and an equal volume of 50:50 Cremophor EL/ethanol (Sigma-Aldrich) was added. After mixing, a 1:10 dilution was made with sterile PBS. Animals were treated with vehicle (PBS/Cremophor EL/ethanol/DMSO), lapatinib, obatoclax, or a combination of lapatinib and obatoclax using oral gavage to a final concentration of 5 mg/kg QD body mass for obatoclax and 100 mg/kg BID for lapatinib for 3 d. *P < 0.05 greater survival than in AR-BT474 cells with vehicle; ^¶P < 0.05 greater survival than vehicle treated WT-BT474 cells. Inset: H&E staining of tumors at the time of animal death. (B) WT-BT474 cells (1 × 10⁶ cells, each animal) were injected into the fourth mammary fat pad. Fourteen days after tumor cell implantation tumors of ~100 mm³ had formed, and animals were segregated into treatment groups. For animal administration, lapatinib and flavopiridol were first dissolved in DMSO, and an equal volume of 50:50 Cremophor EL/ethanol (Sigma-Aldrich) was added. After mixing, a 1:10 dilution was made with sterile PBS. Animals were treated with vehicle (PBS/Cremophor EL/ethanol/DMSO), lapatinib, flavopiridol, or a combination of the drugs using oral gavage to a final concentration of 25 mg/kg QD body mass for flavopiridol and 50 mg/kg BID for lapatinib for 3 d. *P < 0.05 greater survival than in vehicle-treated cells.