PI-3065 (75 mg/kg, p.o.) inhibits the growth of 4T1 tumours in the BALB/c mice without obvious body weight loss[1].
In Vitro
PI-3065 exhibits no inhibition of the growth of 4T1 cells, which do not express detectable levels of p110δ[1].
Kinase Assay
Cell Assay
Animal Administration
Female WT BALB/c mice are orthotopically inoculated in the mammary fat pad on day 0 with 1×105 4T1 cells. Drug (75 mg/kg PI-3065, once daily) or vehicle (0.5% methylcellulose with 0.2% Tween 80) is administered by oral gavage from day -1 (administered 12 h prior to tumour cell inoculation). Tumour growth is monitored weekly by caliper measurement or by measuring luminescence using a Xenogen imaging platform. On day 35, mice are euthanized, tumours and peripheral organs extracted for in vitro luminescence measurement, followed by fixation in 4% PFA and H&E staining. KPC mice are allowed to develop advanced lesions of 5-10 mm (determined by ultrasound imaging) before treatment with vehicle or PI-3065 for a total of 14 days.
References
[1]. Ali K, et al. Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer. Nature. 2014 Jun 19;509(7505):407-11.
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