Sympathetic & beta;(2)( )-adrenergic receptor blockade overcomes docetaxel resistance in prostate cancer

作者全名："Zhang, Mi; Chen, Fangfang; Sun, Xueqing; Huang, Yanping; Zeng, Yan; Chen, Jinying; Wu, Shiqi; Xu, Chen"

作者地址："[Zhang, Mi; Chen, Fangfang; Huang, Yanping; Zeng, Yan; Chen, Jinying; Wu, Shiqi; Xu, Chen] Chongqing Med Univ, Inst Life Sci, 1 Med Coll Rd, Chongqing 400016, Peoples R China; [Sun, Xueqing] Shanghai Jiao Tong Univ, Dept Biochem & Mol Cell Biol, Shanghai Key Lab Tumor Microenvironm & Inflammat, Sch Med, Shanghai, Peoples R China"

通信作者："Xu, C (通讯作者)，Chongqing Med Univ, Inst Life Sci, 1 Med Coll Rd, Chongqing 400016, Peoples R China."

来源：BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001026658800001

JCR分区：Q3

影响因子：2.5

年份：2023

卷号：657

期号：　

开始页：69

结束页：79

文献类型：Article

关键词：0 2-adrenergic receptor; Prostate cancer; Chemotherapy resistance; Apoptosis and autophagy

摘要："Purpose: Due to the limited effective therapies, resistance to docetaxel is ordinarily fatal and remains a critical clinical challenge.02-adrenergic receptor(02-AR)can promote the metastasis and invasion of prostate cancer, but the role in chemotherapy-resistant prostate cancer remains unclear.Methods: By downloading the GEO database in NCBI, the expression of 02-AR in different prostate tissues was analyzed. We constructed docetaxel-resistant prostate cancer cell lines by the method of doseescalation. LC3B-labeled stable cells and shAtg5 knockdown stable cells were constructed by lentivirus infection. The molecular mechanism of 02-AR affecting docetaxel sensitivity through apoptosis and autophage were investigated by flow cytometry, mitochondrial membrane potential and western blot. Then we detected the interaction between autophagy and apoptotic by performing immunoprecipitation assay.Results: We show that restraining the activity of 02-AR sensitized the cell response and reduced the resistance to docetaxel. The mechanism involves the regulation of 02-AR in the cellular response to docetaxel through apoptosis and autophagy via caspase signaling and Atg5/AMPK/mTOR pathway as well as the effect of 02-AR on the crosstalk between apoptosis and autophagy via p38 MAPK and JNK/c-Jun/ FOXO3a signaling pathways.Conclusion: Our data demonstrate that 02-AR inhibitor-induced autophagy and apoptosis contribute to the effectiveness responses to docetaxel in castration-resistant prostate cancer, and in combination with pharmacological agents of 02-AR and autophagy inhibitors may provide a potential therapeutic strategy to enhance the limited capacity of docetaxel to control castration-resistant prostate cancer.& COPY; 2023 Elsevier Inc. All rights reserved."

基金机构：National Natural Science Foundation of China [81402282]

基金资助正文：We thank the National Natural Science Foundation of China (Number 81402282) for the support.