Table 3.

NRF2 cellular targets in ovarian cancer.

Protein Regulated by NRF2	Model Studied	Effect	Ref.
ERα	OVCAR3, ES2, UWB1.289, and TOV112D ovarian cancer cells and HOSEpiC (benign cells)	NRF2 silencing increases ESR1 expression in OVCAR3 and ES2 cells. NRF2 is highly expressed in the ovarian cancer cell lines OVCAR3, ES2, UWB1.289, and TOV112D compared with the benign cell line HOSEpiC. ERα, is reduced in all ovarian cancer cell lines compared to the benign cell line HOSEpiC.	[28]
CD99	A2780, A2780/CDDP, COC1 and COC1/CDDP cells	CD99 is highly expressed in cisplatin-resistant both ovarian cancer cells (A2780/CDDP and COC1/CDDP) and tissues compared to both ovarian cisplatin-sensitive cells (A2780 and COC1) and tissues. CD99 overexpression leads to cisplatin resistance while CD99 knockdown sensitizes ovarian cancer cells to cisplatin. NRF2 silencing leads to decreased CD99 expression and cell viability after cisplatin treatment in cisplatin-resistant cells.	[74]
ErbB2	SKOV3 cells	NRF2 silencing represses NRF2 signaling leading to cell growth G0/G1 phase arrest, tumour growth retardation and a significant decrease of ErbB2 expression in mouse xenografts. ErbB2 downregulation leads to a decrease in pAKT and increase p27 protein, enhancing the effect of NRF2 knockdown in SKOV3 growth.	[76]
AKR1C1 AKR1C2 AKR1C3	SKOV3 cells	NRF2 knockdown decreases AKR1C1-3 expression and increases ROS production after cisplatin treatment. Moreover, NRF2 knockdown increases activation of the pJNK/p38 pathway and decreases phosphorylation of ATF2.	[79]
c-MET EGFR	SKOV3 cells	NRF2 silencing increases miR-206 expression and reduces the levels of c-MET and EGFR inhibiting cell proliferation and increasing doxorubicin effect in SKOV3 cells.	[81]
PGR	OVCAR3, ES2, UWB1.289, HOSEpiC and TOV112D cells	NRF2 is increased and PGR decreased in the ovarian cancer cell lines compared with the benign line (HOSEpiC). NRF2 silencing induces higher PGR mRNA expression in OVCAR3.	[29]
ABCF2	A2780 cells	ABCF2 has a functional antioxidant response element (ARE) in its promoter region that is regulated by NRF2 responsible for cisplatin resistance.	[84]
SLC40A1	cisplatin-sensitive (A2780, COC1, PEO1) and cisplatin-resistant (A2780CP, COC1/DDP, PEO4) cells	Increased levels of NRF2 and reduced levels of SLC40A1 in cisplatin-resistant cells compared with cisplatin-sensitive cells. NRF2 knockdown leads to SLC40A1 overexpression while NRF2overexpression caused SLC40A1 downregulation. SLC40A1 overexpression reverses cisplatin resistance induced by NRF2, while SLC40A1knockdown restores cisplatin resistance and increases iron concentration.	[86]