Jnk in 8

Nude female mice (nu/J #002019, Jackson Labs, Sacramento, CA) at 6 weeks of age were injected orthotopically (L4 mammary gland) with 3×10⁶ MDA-MB-231 TNBC cells in PBS. Nine days later, tumors reached an average volume of 80mm³ and mice were randomized into four groups (n=10 mice per group). Treatment with vehicle, JNK-IN-8 (25mg/kg) (Advanced ChemBlocks, Burlingame, CA), lapatinib (75mg/kg) (MedChem Express, Monmouth Junction, NJ), or JNK-IN-8 and lapatinib combination was administered daily. JNK-IN-8 or its vehicle (2% ethanol and 5% Tween-80 in PBS) were administered by intraperitoneal injection, and lapatinib or its vehicle (0.5% hydroxypropylmethylcellulose and 0.1% Tween-80 in PBS) were administered by oral gavage. Tumors were measured every other day and mice were monitored for signs of distress including significant weight loss, loss of ambulation, or difficulty breathing. Mice with tumors that reached a maximum diameter of 15mm or a maximum volume of 750mm³ were euthanized. A Kaplan-Meier curve is shown where an adverse event represents attainment of the maximal tumor size. No mice died unexpectedly during this experiment and were treated humanely with oversight by the University of Texas IACUC committee (protocol# AUP-2015-00170).

SP600125 (15 mg/kg/d; Selleckchem) or JNK-IN-8 (20 mg/kg/d; MedChemExpress) was given intraperitoneally in vehicle of 4.5% DMSO, 40% PEG400, 5% Tween-80, and 50.5% PBS daily for 12 days.