Figure 8

Impacts of lactic acidosis on cancer cell proliferation or survival in vitro and in vivo.

(a) Lactic acidosis allows 4T1 cells to grow under moderate glucose deprivation. Cells incubated in RPMI-1640 medium containing 0.5 mM glucose without lactic acidosis or with lactic acidosis (20 mM lactate and pH 6.7) are counted at indicated time points. Data represent mean ± SD, n = 3 and are confirmed by 2 independent experiments. (b) Lactic acidosis allows a significantly longer sustainable proliferation with limited supply of glucose. Cells incubated in RPMI-1640 medium containing 6 mM glucose without lactic acidosis or with lactic acidosis (20 mM lactate and pH 6.7) are counted at indicated time points. Data represent mean ± SD, n = 3 and are confirmed by 2 independent experiments. (c–i) Elevating intratumoral pH inhibits tumor growth and promotes tumor necrosis. Sodium bicarbonate administration surrounding tumor areas inhibits 4T1 tumor growth and increases their necrosis. (c–e) Intratumoral glucose and lactate concentration and pH; (f) Body weight curves; (g) Tumor growth curves; (h) Tumor weights on the day of sacrifice; (i) Necrosis in tumors. The n is 5 for each group at the starting point; however, one mouse in the control group dies on day 19. Hence, the images of 4 tumor samples from each group are shown. For detailed experimental procedures refer to Methods. The statistical data represent mean ± SEM. * p < 0.05, ** p < 0.01, *** p < 0.001, compared with control.