Objective: To investigate whether
hypoxia-inducible factor-2α (HIF-2α) affects the
biological behaviors of
hepatoma cells through regulating
stearoyl-CoA desaturase-1 (SCD1) in a hypoxic environment. Methods: HepG2 and SMMC-7721 cells were exposed to 1% O2 to establish the hypoxic models. After
hepatoma cells were stimulated by
hypoxia for 0, 3, 6, 12, and 24 hours, fluorescent quantitative PCR and Western blot were used to measure the
mRNA and
protein expression of HIF-2α and SCD1 over time. HIF-2α interfering plasmids and SCD1 inhibitor
CAY10566 were used to divide the cells into blank group (nomoxia), hypoxic group (1% O2 for 12 h), hypoxic negative control group (negative HIF-2α plasmid+1% O2 for 12 h), hypoxic interference group (HIF-2α interfering plasmid+1% O2 for 12 h), hypoxic CAY group (
CAY10566 10 μmol+1% O2 for 12 h), and hypoxic interference+CAY group (HIF-2α interfering plasmid+CAY10566 10 μmol+1% O2 for 12 h). Western blot was used to measure the
protein expression of HIF-2α and SCD1 in
hepatoma cells, CCK8 assay was used to measure the proliferative capacity of
hepatoma cells,
Annexin-V/PE flow cytometry was used to measure the apoptosis of
hepatoma cells, and transwell invasion assay was used to measure the invasion of
hepatoma cells. A one-way analysis of variance was used to compare the means of multiple samples. Results: Both HepG2 and SMMC-7721 cells showed increasing
mRNA and
protein expression of HIF-2α and SCD1 over the time of hypoxic induction. After the expression of HIF-2α was downregulated in a hypoxic environment,
hepatoma cells showed a significant reduction in the
protein expression of SCD1; inhibition of SCD1 expression had no significant effect on the
protein expression of HIF-2α in
hepatoma cells. After HIF-2α was interfered with and SCD1 expression was inhibited, HepG2 and SMMC-7721 cells showed significantly greater reduction in the
protein expression of SCD1 than those with HIF-2α or SCD1 inhibition alone (0.53±0.04 vs 1.12±0.04 or 1.12±0.04; 0.44±0.10 vs 0.90±0.10 or 0.99±0.13) (HIF-2α: FhepG2 = 1026.89, PhepG2 = 0.00, FSMMC-7721 = 2186.22, PSMMC-7721 = 0.00; SCD1: FhepG2 = 1347.93, PhepG2 = 0.00, FSMMC-7721 = 46.43, PSMMC-7721 = 0.00). Inhibition of the expression of HIF-2α or SCD1 reduced the proliferation and invasion of HepG2 and SMMC-7721 cells and promoted apoptosis (P < 0.05); interference and downregulation of HIF-2α combined with inhibition of SCD1 expression by
CAY10566 achieved significantly greater reductions in proliferation and invasion and a significantly greater increase in apoptosis rate of
hepatoma cells, compared with inhibition of HIF-2α or SCD1 alone (P <0.05). Conclusion: HIF-2α/SCD1 pathway may be one of the important mechanisms for
hypoxia to regulate the energy metabolism of
hepatoma cells and affect their
biological behaviors.