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Intra-Lesional Injection of the Novel PKC Activator EBC-46 Rapidly Ablates Tumors in Mouse Models

Figure 2

EBC-46 efficacy in vivo is independent of tumor cell sensitivity in vitro.

A. Dose response for cell killing by EBC-46 compared to PMA. B16-F0 (circles) or SK-MEL-28 (squares) melanoma cells were treated with the indicated doses of either EBC-46 (blue) or PMA (red) for 4 days, before assay for cell survival using the sulforhodamine B assay. Data shown are mean ± SD from triplicate readings from three independent experiments, n = 3. B. Kaplan Meier analysis of survival of C57BL/6J mice with B16-F0 tumors. Mice with two tumors were treated with single bolus doses of vehicle alone (20% propylene glycol in water; light grey), 50 nmol (30 µg) PMA (mid grey) or 50 nmol (30 µg) EBC-46 (black). Mice were euthanized once the total tumor volume reached 1,000 mm3 per animal. Squares – censored data. Difference between survival following treatment with EBC-46 or PMA was significant (*** p = 0.0004; Log-rank (Mantel-Cox) Test). Data was obtained from 6 mice per group, 2 tumors per mouse; n = 12. C. Kaplan Meier analysis of SK-MEL-28 melanoma tumors reaching >100 mm3 in BALB/c Foxn1nu mice following single treatment with vehicle alone (grey) or 30 µg EBC-46 (black) (***, p<0.0001; Log-rank (Mantel-Cox) Test). Data was obtained from 5 mice per group, 2 tumors per mouse; n = 10. D. Kaplan Meier analysis of MM649 melanoma tumors reaching >100 mm3 in BALB/c Foxn1nu mice following single treatment with vehicle alone (grey) or 50 nmol (30 µg) EBC-46 (black) (***, p<0.0001; Log-rank (Mantel-Cox) Test). Data was obtained from 5 mice per group, 2 tumors per mouse; n = 10.

Figure 2

doi: https://doi.org/10.1371/journal.pone.0108887.g002