Regulations of sevoflurane or propofol on PEDF expression, Erk pathway, and HIF-1α expression
From immunofluorescent staining, it was found that the fluorescent intensity of pigment epithelium-derived factor (PEDF) was decreased in the sevoflurane group but increased in the propofol group compared to naïve control (Fig 4A ). The result was validated using Western blot analysis, which showed the significantly lower expression level of PEDF after sevoflurane exposure (NC vs . S, 1.0 ± 0.1 vs . 0.6 ± 0.2, p < 0.0001, n = 6) but significantly higher after propofol exposure (NC vs . P, 1.0 ± 0.1 vs . 1.2 ± 0.1, p < 0.05, n = 6) (Fig 4D ). Different from PEDF expression levels, the Western blot analysis showed that the expression level ratio of p-Erk1/2 to Erk1/2 was significantly increased in the sevoflurane group (NC vs . S, 1.0 ± 0.1 vs . 1.3 ± 0.2, p < 0.05, n = 6), but decreased in the propofol group compared to the control (NC vs . P, 1.0 ± 0.1 vs . 0.7 ± 0.2, p < 0.05, n = 6) (Fig 4E ). Similarly, the fluorescent staining showed SKOV3 cells administered with sevoflurane had a higher intensity of hypoxia-inducible factor 1-alpha (HIF-1α) than the naïve control, while those of the propofol group had a lower intensity of HIF-1α than control (Fig 4B ). From Western blot analysis, it was also found that the expression level of HIF-1α was significantly increased after cancer cells administered with sevoflurane (NCvs . S, 1.0 ± 0.3 vs . 1.5 ± 0.5, p < 0.05, n = 6), but significantly decreased after propofol treatment compared to the control (NC vs. S, 1.0 ± 0.3 vs. 0.4 ± 0.3, p < 0.05, n = 6) (Fig 4F ).