Fig. 8

In vivo treatment with acetazolamide acidifies the microenvironment of murine ErbB2-induced breast cancer tissue, lowers lactate concentrations, and accelerates tumor growth. A In vivo pH measurements performed with a pH-sensitive microelectrode (n = 8). “Core” was defined as the most acidic region encountered during stepwise impalement with the electrode. The mice had been treated with an intraperitoneal injection of 50 mg/kg acetazolamide (ATZ) or equivalent volume of vehicle 30 min prior to recordings. Data were compared by repeated-measures two-way ANOVA. B Exemplary postmortem tumor images and in vivo ErbB2-induced breast cancer growth curves for mice treated with 40 mg/kg ATZ by daily intraperitoneal injections compared to mice receiving equivalent volume of vehicle (n = 17). Data were fitted to a second order polynomial function, and the best-fit parameters were compared by extra sum-of-squares F-test. The scale bar represents 5 mm; both images are shown at the same magnification. C–H Tumor glycolytic metabolism evaluated by microdialysis. Interstitial or serum [lactate] (C–E) and [glucose] (F–H) measured 1 h after initiation of ATZ or vehicle administration (n = 8–13). Data were compared by two-way ANOVA followed by Šidák’s post-test (panel C, E, F, and H) or unpaired two-tailed Student’s t tests (panel D and G). *P < 0.05, **P < 0.01, ***P < 0.001, NS: not significantly different vs. normal tissue (panel C and F), vehicle (panel A, B, D, E, G, and H), or as indicated