STC-1 is involved in anti-hypoxia proliferative balance of renal cancer cells by down-regulation of intracellular Ca2+ and HIF-1α levels

Abstract

To investigate effects of stanniocalcin-1 (STC-1) on proliferation balance under hypoxic condition in renal cancer cells and its mechanism. Hypoxic model was induced on renal cancer GRC-1 cells (Group H), the cells were treated with STC-1 protein at concentrations of 0.1 nmol/L (H1), 0.5 nmol/L (H2), 1.0 nmol/L (H3), or normal saline (H0) for 48 h， respectively. Cells proliferation was measured by MTT assay; mRNA and protein expressions of hypoxia inducible factor 1α (HIF-1α) and STC-1 in GRC-1 cells were detected by RT-PCR and ELISA, respectively; the intracellular levels of Ca2+ and adenosine triphosphate (ATP) were determined by fluorescence spectrophotometry and spectrophotometry, respectively. The expression of HIF-1α, STC-1 and Ca2+ levels were increased in GRC-1 cells under hypoxia condition; STC-1 reversed these changes in a dose-effect manner. Hypoxia significantly inhibited cell proliferation and the generation of ATP in GRC-1 cells and exogenous STC-1 reversed the effects of hypoxia; ATP generation increased gradually with increasing STC-1 concentration, but the cell proliferation was reduced. Exogenous STC-1 can promote the proliferation of renal cancer cells in hypoxia condition by reducing HIF-1α expression and Ca2+ content and increased ATP production, but the progressive inhibition of HIF-1 α hindered the renal carcinoma cell proliferation further, which indicates that STC-1 may be involved in anti-hypoxia proliferative balance of renal cancer cells.