Abstract: Objective To investigate the role of sphingosine kinase 1 (SphK1) in regulating the proliferation of hypoxia-exposed
glioma cells in vitro and explore the possible molecular mechanisms. Methods Human glioblastoma U87MG cells was
transfected with specific small interfering RNA (siRNA) constructs targeting SphK1, and the efficiency of SphK1 knockdown
was validated by real-time PCR and Western blotting. The cells transfected with SphK1 siRNA and with a negative control
siRNA were then exposed to 3% oxygen or 150 μmol/L CoCl2 to induce hypoxia. The cell proliferation and cell cycle changes
following the exposure were evaluated with the Cell Counting Kit-8 and flow cytometry, respectively, and the intracellular Ca2+
changes were monitored using Flou-4/AM under an inverted laser scanning confocal microscope. Results SphK1 knockdown
significantly reduced hypoxia-induced calcium reflux and suppressed the cell proliferation. Application of OAG, an activator
of calcium channels, however, obviously enhanced the cell proliferation under hypoxia. Conclusion SphK1 promotes the
proliferation of glioma cells under hypoxia via regulating calcium signaling.