Fig. 6.

β3-AR blockade reduces tumor growth in A/J mice through the involvement of SK2/S1P₂ signaling axis. Neuro-2A cells were injected subcutaneously (1 × 10⁶ cells) in the flank of A/J female mice. When a palpable tumor mass was formed (6 days), mice were treated with Vehicle (i.p.), SR59230A 10 mg/kg (i.p.) alone or in combination with CYM5520 5 mg/kg (i.p.) and ABC294640 30 mg/kg (p.o.). a After 8 days of treatment, mice were sacrificed and tumor mass excised; images of tumors are representative of the final size of all tumors respectively for each treatment (n = 6 for group). b Tumor growth rate obtained by measuring tumor size of the mass calculated as Volume = [(length × widht)²/2] in Vehicle (n = 6), SR59230A (n = 6), CYM5520 (n = 6) and SR59230A+CYM5520 (n = 6) (top) and Vehicle (n = 6), SR59230A (n = 6), ABC294640 (n = 6) and SR59230A+ABC294640 (n = 6) (bottom). Vehicle and SR tumor size results reported in (top) and (bottom) graphs are referred to the same tumors. Significance was calculated by two-way ANOVA analysis followed by Bonferroni’s post hoc test (*P < 0.05, **P < 0.01, ****P < 0.0001; ^##P < 0.01 SR+CYM vs. SR, ^####P < 0.0001 SR+CYM vs. SR; ^§§§P < 0.001, ^§§§§P < 0.0001 Vehicle vs. ABC). c Tumor weight at the end point of the experiment (14 days) (n = 6 per group). Results are reported as individual dots with mean (central line) ±SD. Significance was calculated by two-way ANOVA analysis followed by Bonferroni’s post hoc test (****P < 0.0001; ^##P < 0.01 SR+CYM vs. SR; ^§§§§P < 0.0001 ABC vs. Vehicle). d S1P measurement in tumors of Vehicle- (n = 3), SR59230A- (n = 3) and ABC294640-treated mice (n = 3). Results are reported as mean ± SD. Significance was calculated by one-way ANOVA analysis followed by Bonferroni’s post hoc test (**P < 0.01, ***P < 0.001)