Dataset: Transcription profiling of human A549 induced tumours in mice treated with PCI-5002, PCI-5003, or control vehicle
We have demonstrated that water-soluble zinc ionophores can be administered to mice at relatively high doses and inhibit the growth of...
We have demonstrated that water-soluble zinc ionophores can be administered to mice at relatively high doses and inhibit the growth of A549 lung cancer cells grown in xenograft models. Gene expression profiles of tumor specimens harvested from mice four hours after treatment confirmed that the activation of stress responsive genes occurs in vivo. These findings lead us to propose that the pharmacologic delivery of zinc to tumors using water solubilized ionophores is a potential approach to cancer therapy. Experiment Overall Design: 1.25 million A549 cells were injected subcutaneously/intramuscularly into the right hind flank of 6 week old CD-1 nude mice that had been irradiated with 4 Gy of total body irradiation from a 137Cs radiation source one day prior to tumor implantation. When the average size of tumors reached approximately 100 mm3, mice were randomized by tumor size to treatment groups, typically containing 6-8 mice per group. Tumor and body weight measurements were performed three times per week. Tumor volume was calculated using the equation V (mm3) = a x b2/2, where a is the largest diameter and b is the smallest diameter. No significant body weight loss was observed. To perform gene expression profiling, mice were treated intravenously with one dose (100 μmol/kg) PCI-5002, PCI-5003, or control vehicle (4 mice per group) when the average A549 tumor size reached 500 mm3. After four hours, tumors were harvested and snap frozen immediately on dry ice. Tumor tissue was homogenized, and total RNA was isolated and subjected to analysis using Human Genome U133 Plus 2.0 Arrays as described above.
- Dec.12, 2014
- Sep.21, 2014