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Evaluation of JQ1 Combined With Docetaxel for the Treatment of Prostate Cancer Cells in 2D-and 3D-Culture Systems

文献类型：期刊论文

作者Xu, Yipeng3,4,5; Pachnikova, Gabriela1,2,6,7; Przybilla, Dorothea1,2,6,7; Schafer, Reinhold1,2,6,7; Cui, Yingying1,2,6,7; Zhou, Dan1,2,6,7; Chen, Zihao8; Zhao, An5,9; Keilholz, Ulrich1,2,6,7,10
刊名FRONTIERS IN PHARMACOLOGY
出版日期2022-02-03
卷号13
关键词Prostate Cancer JQ1 Docetaxel Combination Treatment 3D Culture Spheroid
DOI10.3389/fphar.2022.839620
通讯作者Zhao, An(zhaoan@zjcc.org.cn) ; Keilholz, Ulrich(ulrich.keilholz@charite.de)
英文摘要Introduction: Prostate cancer (PCa) is dependent on coupled androgen-androgen receptor (AR) signaling for growth and progression. Significant efforts have been made in this research field, as hormonal therapies have greatly improved the survival of patients with metastatic PCa (mPCa). The drug treatment agent JQ1, which potently abrogates bromodomain 4 (BRD4) localization to the AR target loci and therefore significantly impairs AR-mediated gene transcription, is a potent therapeutic option for patients with advanced PCa. In this study, we aimed to investigate the inhibitory effect of JQ1 combined with docetaxel on PCa cells in vitro for the first time. Furthermore, the 3D spheroid culture system was modeled to more accurately simulate the response of PCa cells to drugs.Methods: We established and measured 3D LNCaP spheroids in vitro in order to evaluate the susceptibility of 2D- and 3D-cultured LNCaP cells exposed to the same anti-cancer drug.Results: We demonstrated that JQ1 was an effective drug for promoting cell inhibition after docetaxel treatment in 2D- and 3D- cultured LNCaP cells. Inhibition of 3D cultured formation in the combined treatment group was significantly higher than that in docetaxel or JQ1 alone. Under the same conditions of drug solubility, the drug resistance of 3D spheroids was significantly higher than that of 2D cells. Moreover, d(max) and lg volume were suitable parameters for LNCaP cells/spheroid size displaying and evaluating cell viability.Conclusion: 3D cultured spheroids of PCa are an effective tool for studying PCa drug trials. JQ1 combined with docetaxel may be an effective treatment for advanced PCa. This combination therapy strategy deserves further evaluation in clinical trials.
WOS关键词CASTRATION ; ESTRAMUSTINE ; COMBINATION ; CARCINOMA
WOS研究方向Pharmacology & Pharmacy
语种英语
出版者FRONTIERS MEDIA SA
WOS记录号WOS:000759856300001
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/127985]  
专题中国科学院合肥物质科学研究院
通讯作者Zhao, An; Keilholz, Ulrich
作者单位1.Humboldt Univ, Berlin, Germany
2.Berlin Inst Hlth, Berlin, Germany
3.Univ Chinese Acad Sci, Canc Hosp, Dept Urol, Zhejiang Canc Hosp, Hangzhou, Peoples R China
4.Key Lab Zhejiang Prov Aptamers & Theranost, Hangzhou, Peoples R China
5.Chinese Acad Sci, Inst Basic Med & Canc IBMC, Hangzhou, Peoples R China
6.Charite Univ Med Berlin, Comprehens Canc Ctr, Berlin, Germany
7.Free Univ Berlin, Berlin, Germany
8.Southern Med Univ, Dept Urol, Guangzhou, Peoples R China
9.Univ Chinese Acad Sci, Canc Hosp, Expt Res Ctr, Zhejiang Canc Hosp, Hangzhou, Peoples R China
10.German Canc Consortium DKTK, Heidelberg, Germany
推荐引用方式
GB/T 7714		 Xu, Yipeng,Pachnikova, Gabriela,Przybilla, Dorothea,et al. Evaluation of JQ1 Combined With Docetaxel for the Treatment of Prostate Cancer Cells in 2D-and 3D-Culture Systems[J]. FRONTIERS IN PHARMACOLOGY,2022,13.
APA Xu, Yipeng.,Pachnikova, Gabriela.,Przybilla, Dorothea.,Schafer, Reinhold.,Cui, Yingying.,...&Keilholz, Ulrich.(2022).Evaluation of JQ1 Combined With Docetaxel for the Treatment of Prostate Cancer Cells in 2D-and 3D-Culture Systems.FRONTIERS IN PHARMACOLOGY,13.
MLA Xu, Yipeng,et al."Evaluation of JQ1 Combined With Docetaxel for the Treatment of Prostate Cancer Cells in 2D-and 3D-Culture Systems".FRONTIERS IN PHARMACOLOGY 13(2022).

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来源：合肥物质科学研究院

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