Midkine Mediates Intercellular Crosstalk between Drug-Resistant and Drug-Sensitive Neuroblastoma Cells In Vitro and In Vivo

Figure 6

Effect of midkine cytoprotection on growth of wild type human neuroblastoma tumors in vivo. Mice were injected with drug-sensitive human neuroblastoma cells (SK-N-SH GFP-WT) and (a) drug-resistant human neuroblastoma cells (SK-N-SH DoxR) or (b) midkine transfected cells (SK-N-SH HMK) at various ratios (GFP-WT : DoxR or GFP-WT : HMK). Once the tumors were palpable, the mice received injections of doxorubicin (2.5 mg/kg) intraperitoneally every 3 days for a total of 3 doses. Tumor volumes were measured every 3 days for up to 3 weeks. Tumor growth curves in the different groups were generated. Each data point in the growth curve represents the mean of 7 determinations ± SE. *𝑃<0.05; **𝑃<0.01; ***𝑃<0.001. (c and d) Apoptotic GFP-WT cells were measured by TUNEL assay in tumor sections. The histogram represents a summary data.

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