Fig. 4. DDAs kill Lapatinib-resistant cancer cells.
a Micrographs of liver metastases and lung tumor emboli generated in mice by a HCI-012 cell line selected for liver metastasis (LVM) and growth in the presence of 10 µM Lapatinib (LR10). b Immunoblot analysis of parental liver metastatic HCI-012 cells (012/LVM), or sublines selected for growth in 5 (LR5) or 10 µM (LR10) Lapatinib. c MTT cell viability assays on the indicated cell lines after treatment for 72 h with increasing concentrations of Lapatinib (left panel) or tcyDTDO (right panel). d Immunoblot analysis of the indicated cell lines treated for 24 h with the specified concentrations of Lapatinib, tcyDTDO, or Lapatinib + tcyDTDO. e Tumor-bearing mice were randomly separated into two groups of four mice each and treated for 5 days with either vehicle (DMSO) or 20 mg/kg of tcyDTDO. Mice were killed at day 5 (3 h after treatments) and tumor samples and metastatic lesions were collected for hematoxylin and eosin (H&E) staining and cleaved caspase 3 staining. Abbreviations used include M, muscle tissue; T, tumor tissue; SFs, stromal fibroblasts. f MTT cell viability assays performed after a 72-h treatment with 10 µM Lapatinib, 10 µM tcyDTDO, 25 ng/ml TRAIL, or tcyDTDO + TRAIL. g Immunoblot analysis of 012/LVM/fLuc cells treated for 24 h as specified. 012/LVM/fLuc cells were labeled using a lentiviral firefly luciferase vector as described in the “Materials and methods” section.