Lactate induces normoxic HIF-1α protein stabilization in oxidative tumor cells, not in Warburg tumor cells.

<p>(A) Lactate release in the supernatant of SiHa and WiDr TCs was measured using a CMA600 enzymatic analyzer after 24-h of culture in fresh medium. ***<i>p</i> = 0.0002; <i>n</i> = 4. (B–G) HIF-1α and β-actin protein expression was detected using Western blotting in the lysates of oxidative SiHa or Warburg WiDr TCs. The upper panels show representative experiments and the graphs HIF-1α protein expression normalized to β-actin levels. (B) SiHa and WiDr cells were untreated to detect basal HIF-1α protein expression. *<i>p</i> = 0.0414; <i>n</i> = 3–4. (C) SiHa TCs were cultured during 24-h under hypoxia (1% O₂) or not. *<i>p</i> = 0.011; <i>n</i> = 3. (D) As in (C) but with WiDr TCs. **<i>p</i> = 0.0057; <i>n</i> = 5. (E) SiHa TCs were cultured during 24-h in the presence of 10 mM lactate or not. **<i>p</i> = 0.0029; <i>n</i> = 4. (F) As in (E) but with WiDr TCs. <i>ns</i>, <i>p</i> = 0.1449; <i>n</i> = 8. (G) SiHa TCs were exposed to increasing doses of lactate during 24-h. *<i>p</i><0.05, **<i>p</i><0.01 <i>versus</i> 0 mM lactate condition; <i>n</i> = 9–11. (H) SiHa TCs were exposed to 10 mM lactate during increasing periods of time. *<i>p</i><0.05, **<i>p</i><0.01 <i>versus</i> time 0; <i>n</i> = 3.