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Abstract Title:

Stigmasterol sensitizes endometrial cancer cells to chemotherapy by repressing Nrf2 signal pathway.

Abstract Source:

Cancer Cell Int. 2020 ;20:480. Epub 2020 Oct 6. PMID: 33041661

Abstract Author(s):

Hong Liao, Dan Zhu, Mingzhu Bai, Huifen Chen, Shihuan Yan, Jing Yu, Huiting Zhu, Wenxin Zheng, Guorong Fan

Article Affiliation:

Hong Liao

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 remains unclarified.

Methods: Immunohistochemistry staining was used to detect the expression of Nrf2 in normal patient and endometrial cancer patient. Stable transfection Ishikawa cell line with high level of Nrf2 was established to evaluate its role in chemoresistance. Dot blot assays were used to assess global hydroxymethylation level after stigmasterol treatment. Cellular growth profile 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, stigmasterol has been identified as a novel Nrf2 inhibitor. It enhanced the sensitivity of endometrial cancer cells to cisplatin, and the underlying mechanism is that stigmasterol declines the Nrf2 protein level.

Conclusions: Our findings identified stigmasterol as a new potential inhibitor of Nrf2 and highlight a critical role of stigmasterol in overcoming chemoresistance in endometrial cancer therapy.

Study Type : In Vitro Study

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Sayer Ji
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