Figure 1

Metformin promotes antitumor activity of C-REV on both the injected and contralateral sides in Pan02 tumor-bearing mice. (a) The scheme shows the schedule of C-REV and metformin treatment in C57BL/6 bilateral tumor-bearing mice. Female Six- to seven-week-old C57BL/6 mice were subcutaneously inoculated with Pan02 in both flanks. When tumor size reached around 100 mm3, mice were randomly divided into four groups (n = 4 mice) with an equal average tumor volume among the groups. C-REV was injected three times (1 × 106 pfu) with three days intervals (D0, D3, and D6) on only one side (injected side) and metformin was continuously supplied in the drinking water (5 mg/ml) after C-REV treatment. Tumor sizes on both sides of tumor were measured twice a week. This experiment was conducted four times, yielding similar results. (b) Representative tumor growth in Pan02 tumor models after treatment. Data are presented as mean ± SD. Two-way ANOVA followed by Tukey’s multiple comparisons tests were performed. (c) Representative mouse survival in Pan02 tumor models after treatment (n = 9). For the evaluation of survival, the death event was defined when the total tumor size reached 2000 mm3. Survival analysis was performed using the Kaplan–Meier method. The log-rank test was used for the statistical comparison of the curves. (b) and (c) are from different experiments. * p < 0.05, ** p < 0.01, **** p < 0.0001.