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Orphan Nuclear Receptor RORγ Confers Doxorubicin Resistance in Prostate Cancer

Orphan Nuclear Receptor RORγ Confers Doxorubicin Resistance in Prostate Cancer

Menghan Gao, Lang Guo, Hong Wang, Jialuo Huang, Fanghai Han, Songtao Xiang, Junjian Wang

Cell Biol Int. 2020 Jun 25.

PMID: 32584473

Abstract:

Prostate cancer (PCa) is a malignant tumor with an extremely high prevalence. Doxorubicin is the first-line clinical treatment for castration-resistant PCa. In clinical, relapse is almost inevitable due to the cancer cells' increasing resistance to doxorubicin. Our previous studies have revealed that retinoic acid-related orphan nuclear receptor γ (RORγ) is a key protein for cancer progression and a promising target for PCa therapy. Though, RORγ's role and mechanism in doxorubicin-resistant prostate cancer remain unclear. To study the mechanism of doxorubicin resistance, we generated a doxorubicin-resistant PCa cell line C4-2B (C4-2B DoxR) in this study, by culturing cells in an increasing doxorubicin concentration. Here we show that RORγ expression was up-regulated in C4-2B DoxR cells compared with that in normal C4-2B cells. The RORγ-stably-overexpressing PCa cell line constructed by lentiviral transfection showed an obvious improvement in doxorubicin resistance and a trend toward castration-resistance. Furthermore, RORγ-specific small molecule inhibitors XY018, GSK805, and SR2211 can significantly inhibit the proliferation of C4-2B DoxR cells and promote their apoptosis. Collectively, these results have demonstrated the correlation between the up-regulation of RORγ and the development of PCa's doxorubicin resistance, thus providing new ideas for solving the problem of chemotherapy drug resistance in PCa. This article is protected by copyright. All rights reserved.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1359164116	SR2211		1359164-11-6	Price

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