Inhibitory Effect of Etravirine, a Non-Nucleoside Reverse Transcriptase Inhibitor, via Anterior Gradient Protein 2 Homolog Degradation against Ovarian Cancer Metastasis

非核苷逆转录酶抑制剂依曲韦林通过前梯度蛋白2同源物降解对卵巢癌转移的抑制作用

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作者:Thanh Truong Giang Ly, Jisoo Yun, Jong-Seong Ha, Yeon-Ju Kim, Woong-Bi Jang, Thi Hong Van Le, Vinoth Kumar Rethineswaran, Jaewoo Choi, Jae-Ho Kim, Sang-Hyun Min, Dong-Hyung Lee, Ju-Seok Yang, Joo-Seop Chung, Sang-Mo Kwon

Abstract

Anterior gradient protein 2 homolog (AGR2), an endoplasmic reticulum protein, is secreted in the tumor microenvironment. AGR2 is a member of the disulfide isomerase family, is highly expressed in multiple cancers, and promotes cancer metastasis. In this study, we found that etravirine, which is a non-nucleoside reverse transcriptase inhibitor, could induce AGR2 degradation via autophagy. Moreover, etravirine diminished proliferation, migration, and invasion in vitro. Moreover, in an orthotopic xenograft mouse model, the combination of etravirine and paclitaxel significantly suppressed cancer progression and metastasis. This drug may be a promising therapeutic agent for the treatment of ovarian cancer.

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