Abstract
Background: Chemoresistance reduces the 5-year survival rate of endometrial cancer patient, which is the current major obstacle for cancer therapy. Increasing evidence state that Nrf2 contributes to chemoresistance in several kinds of cancer. However, its role in endometrial cancer cells need further study.Methods: Immunohistochemistry was used to detect the expression of Nrf2 in healthy patient and endometrial cancer patient. Nrf2 overexpressed stable transfection cell line was established to evaluated its role in chemoresistance. Dot blot assays were used to assess global hydroxymethylation levels after stigmasterol treatment. Cellular growth activation was detected by CCK8 assay. Western blot was used to evaluate the changes of the target molecules after various treatments.Results: Nrf2 is overexpressed in endometrial cancer tissues compared with the normal endometrium. Overexpression of Nrf2 resulted in decrease sensitivity to cisplatin. In addition, a novel Nrf2 inhibitor, stigmasterol, has been identified, which enhanced the sensitivity to cisplatin, and the mechanism is that stigmasterol declines the Nrf2 protein level.Conclusions: Our data identify stigmasterol as a novel potential inhibitor of Nrf2 and highlight a critical role of stigmasterol in inhibiting chemoresistance in cisplatin combination therapy.
Characterization of a 54 kDa, α1Antitrypsin-like Protein Isolated from Ascitic Fluid of an Endometrial Cancer Patient