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Dual targeting of estrogen receptor a and estrogen-related receptor [alpha]: a novel endocrine therapy for endometrial cancer

Background: Endometrial cancer (EC) is a hormone dependent carcinoma that may involve complex molecular mechanisms. Endocrine therapy by blocking the estrogen and estrogen receptor a (ER[alpha]) has been effective in breast cancer, while it is still controversial in EC. Recently, estrogen-related re...

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Bibliographic Details
Published in:OncoTargets and therapy 2019-08, p.6757
Main Authors: Mao, Xiaodan, Dong, Binhua, Gao, Min, Ruan, Guanyu, Huang, Meimei, Braicu, Elena Loana, Sehouli, Jalid, Sun, Pengming
Format: Article
Language:English
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Summary:Background: Endometrial cancer (EC) is a hormone dependent carcinoma that may involve complex molecular mechanisms. Endocrine therapy by blocking the estrogen and estrogen receptor a (ER[alpha]) has been effective in breast cancer, while it is still controversial in EC. Recently, estrogen-related receptor a (ERR[alpha]) was proven to be another endocrine therapy target. Methods: The anti-tumor effect of selective estrogen receptor modulators (SERMs) and XCT790 (XCT) used alone or in combination were evaluated in both of ER[alpha]-positive (ER[alpha]+) and ER[alpha]-negative (ER[alpha]-) EC cells. ER[alpha] and ERR[alpha] mRNA were tested by qPCR, while the protein was detected by Western blot. The proliferation was tested by MTS and cell cycle, apoptosis rate were analyzed by flow cytometry. Results: A relatively high dose (10 [micro]M) of tamoxifen (TAM) suppressed the expression of ER[alpha] and ERR[alpha] in two types of EC cells. However, 10 [micro]M raloxifene (RAL) exhibited no effect on ER[alpha] and ERR[alpha], while 10 [micro]M XCT down regulated ERR[alpha] specifically, but not ER[alpha] in all EC cells. When dual targeting on ER[alpha] and ERR[alpha] by combining TAM with XCT, the proliferation inhibitory effect and apoptosis reached the strongest in all EC cells (P
ISSN:1178-6930
1178-6930
DOI:10.2147/OTT.S216146