Management of prostate cancer by targeting 3βHSD1 after enzalutamide and abiraterone treatment.
Management of prostate cancer by targeting 3βHSD1 after enzalutamide and abiraterone treatment.
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恩杂鲁胺和阿比特龙治疗后靶向 3βHSD1 的前列腺癌管理
DOI：
10.1016/j.xcrm.2022.100608
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发表时间：
2022-05-17
影响因子：
14.3
通讯作者：
Li, Zhenfei
中科院分区：
文献类型：
--
作者：
Mei, Zejie;Yang, Tao;Liu, Ying;Gao, Yuanyuan;Hou, Zemin;Zhuang, Qian;He, Dongyin;Zhang, Xuebin;Tan, Qilong;Zhu, Xuyou;Qin, Yingyi;Chen, Xi;Xu, Chengdang;Bian, Cuidong;Wang, Xinan;Wang, Chenyang;Wu, Denglong;Huang, Shengsong;Li, Zhenfei
前列腺癌治疗需要新的策略来克服对阿比特龙和恩杂鲁胺的耐药性。在这里，我们表明，阿比特龙和恩杂鲁胺治疗后 3βHSD1 的增加对于耐药性至关重要，而生物鸡宁 A (BCA) 作为 3βHSD1 的抑制剂，克服了耐药性。细胞系、活检样本和长期接受恩杂鲁胺或阿比特龙治疗后的患者中，3βHSD1 活性增加。由 3βHSD1 介导的类固醇生成增强足以损害恩杂鲁胺功能。在患者中，阿比特龙代谢加速导致血浆阿比特龙随着疾病进展而下降。 BCA 单独或与阿比特龙和恩杂鲁胺一起抑制 3βHSD1 并抑制前列腺癌的发展。大豆黄酮是一种源自饮食的 BCA 类似物，与较高的阿比特龙血浆浓度相关，并可防止阿比特龙耐药患者的前列腺特异性抗原 (PSA) 增加。总体而言，我们的结果表明，3βHSD1 是克服耐药性的一个有希望的靶点，即使在阿比特龙和恩杂鲁胺耐药后，BCA 作为 3βHSD1 抑制剂也能抑制疾病进展。增加 3βHSD1 会损害阿比特龙和恩杂鲁胺的功效 加速阿比特龙代谢促进耐药性 生物鸡蛋白 A 抑制 3βHSD1 以调节雄激素和阿比特龙代谢 生物鸡蛋白 A 抑制阿比特龙耐药患者的 PSA 增加 Mei 等人。即使在阿比特龙和恩杂鲁胺耐药后，3βHSD1 仍然是前列腺癌治疗的一个有希望的靶点。恩杂鲁胺和阿比特龙长期治疗后3βHSD1的活性增加。 Biochanin A 可抑制 3βHSD1 活性并抑制前列腺癌进展，为进一步的疾病管理和饮食建议提供线索。
Novel strategies for prostate cancer therapy are required to overcome resistance to abiraterone and enzalutamide. Here, we show that increasing 3βHSD1 after abiraterone and enzalutamide treatment is essential for drug resistance, and biochanin A (BCA), as an inhibitor of 3βHSD1, overcomes drug resistance. 3βHSD1 activity increases in cell lines, biopsy samples, and patients after long-term treatment with enzalutamide or abiraterone. Enhanced steroidogenesis, mediated by 3βHSD1, is sufficient to impair enzalutamide function. In patients, accelerated abiraterone metabolism results in a decline of plasma abiraterone as disease progresses. BCA inhibits 3βHSD1 and suppresses prostate cancer development alone or together with abiraterone and enzalutamide. Daidzein, a BCA analog of dietary origin, is associated with higher plasma abiraterone concentrations and prevented prostate-specific antigen (PSA) increases in abiraterone-resistant patients. Overall, our results show that 3βHSD1 is a promising target to overcome drug resistance, and BCA suppresses disease progression as a 3βHSD1 inhibitor even after abiraterone and enzalutamide resistance. Increasing 3βHSD1 impairs the efficacy of abiraterone and enzalutamide Accelerated abiraterone metabolism promotes drug resistance Biochanin A inhibits 3βHSD1 to regulate androgen and abiraterone metabolism Biochanin A inhibits PSA increases in abiraterone-resistant patients Mei et al. identifies 3βHSD1 as a promising target for prostate cancer treatment even after abiraterone and enzalutamide resistance. The activity of 3βHSD1 increases after long-term treatment of enzalutamide and abiraterone. Biochanin A suppresses 3βHSD1 activity and inhibits prostate cancer progression, shedding light on further disease management and dietary advice.
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影响因子：
28.4
作者：
Almassi, Nima;Reichard, Chad;Sharifi, Nima
通讯作者：
Sharifi, Nima
影响因子：
3.2
作者：
Hahn, Andrew W.;Gill, David M.;Agarwal, Neeraj
通讯作者：
Agarwal, Neeraj
DOI：
10.1016/j.jsbmb.2021.105859
发表时间：
2021-03-19
影响因子：
4.1
作者：
Hou, Zemin;Yang, Tao;Li, Zhenfei
通讯作者：
Li, Zhenfei
影响因子：
64.5
作者：
Chang KH;Li R;Kuri B;Lotan Y;Roehrborn CG;Liu J;Vessella R;Nelson PS;Kapur P;Guo X;Mirzaei H;Auchus RJ;Sharifi N
通讯作者：
Sharifi N
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W