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Abstract To investigate the influence of ginkgo biloba regulating nuclear factor E2 related factor 2 (Nrf2)/non glycosylated xCT (SLC7A11) /glutathione peroxidase 4 (GPX4) on the proliferation, apoptosis, and iron death of ovarian cancer (OC) cells. Methods: SKOV3 cells in logarithmic growth phase were selected in study group and in control group. The SKOV3 cells in the study group were divided in group A (cells with the treatment of Nrf2 activator sulforaphane (SFN) of 20 μmol), and group B1 (cells with the treatment of low-concentration ginkgetin of 2.5 μM), group B2 (cells with the treatment of medium-concentration ginkgetin of 5 μM), group B3 (cells with the treatment of high-concentration ginkgetin of 10μM), group C (cells with the treatment of high-concentration ginkgetin of 10μM combined with SFN of 20μmol). And the cells in the control group did not given treatment. The proliferation rate of SKOV3 cells in each group was detected by MTT method. The protein expression levels of Nrf2, SLC7A11, and GPX4 in SKOV3 cells in these groups were detected by Western blot. The mRNA expression levels of iron death factors SLC7A11 and GPX4 in SKOV3 cells were detected by qRT-PCR. The apoptosis rate of SKOV3 cells in each group was detected by flow cytometry. The iron level of SKOV3 cells in these groups was detected by the kit. The protein expression levels of Nrf2, SLC7A11 and GPX4 in SKOV3 cells in these groups were detected by Western blot. Results: The proliferation rate (124.71±12.49%), the expression levels of Nrf2 (1.15±0.12), SLC7A11 (1.58±0.16), and GPX4 (1.08±0.11) of the cells in the study group were all significantly higher than those of the cells in the control group. The apoptosis rate was (4.01±0.41%), the iron level (24.73±2.48) of the cells in the study group were all significantly lower than those of the cells in the control group (P＜0.05). The proliferation rates of the cells in group B1, group B2, and group B3 were 74.22±7.43%, 51.03±5.11%, and 35.23±3.53%, respectively, the Nrf2 level of the cells in group B1, group B2, and group B3 were 0.62±0.07, 0.41±0.05, and 0.18±0.02, respectively, the SLC7A11 level of the cells in group B1, group B2, and group B3 were 0.56±0.06, 0.37±0.04, and 0.16±0.02, respectively, the GPX4 level of the cells in group B1, group B2, and group B3 were 0.61±0.07, 0.43±0.05, and 0.21±0.03, respectively, which had decreased significantly. The apoptosis rate of the cells in group B1, group B2, and group B3 were 14.55±1.46%, 28.17±2.82%, and 42.01±4.21%, respectively, which had increased gradually, and the iron level of cells in group B1, group B2, and group B3 were 48.99±4.91, 60.83±6.10, and, 77.87±7.79, respectively, which had increased gradually (all P＜0.05). The proliferation rate, and the levels of Nrf2, SLC7A11, and GPX4 of cells in group C were 65.09±6.51%, 0.48±0.05, 0.46±0.05, and 0.55±0.06, respectively, which had significantly different from those of the cells in group A and in group B3 (all P＜0.05). Conclusion: Ginkgetin can inhibit the proliferation of OC cell of SKOV3 line, induce its apoptosis and iron death, which may be related to the inhibition of Nrf2/SLC7A11/GPX4 signal pathway.
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