机构：[a]Departments of Urology, Institute of Urology,West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China四川大学华西医院[b]Departments of Neurology, Stroke Clinical Research Unit, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China四川大学华西医院
Acquired docetaxel (Doc) resistance in hormone-refractory prostate cancer (HRPC) remains an ongoing clinical challenge, resulting in failed chemotherapy and tumor recurrence. However, the mechanism of Doc-resistance development in prostate cancer cells is still unclear. Here, we observed a subpopulation of prostate cancer cells, in both Doc-resistant cell lines and the tumors of patients with HRPC, which show stem cell markers and greater tumorigenic potential. Those stem-like prostate cancer cells show high expression of ABCB1, which encodes multidrug resistance-related protein P-glycoprotein, leading to the Doc-resistance in prostate cancer. Moreover, we found that Notch signaling pathway activation in Doc-resistant cell lines and tumor tissues of patients with HRPC correlated with tumorigenicity and the development of Doc resistance. Here, we revealed that a combination of Doc and a Notch signaling inhibitor overcomes Doc resistance and increases the survival of mice with Doc-resistant xenografts. Therefore, targeting the Notch signaling pathway may be a promising strategy to overcome the Doc-resistant cancer in the clinic.
基金：
This study was supported
by the National Key Research and Development
Program of China (Grant no. 2017YFC0908003), the
National Natural Science Foundation of China (Grant
nos 81500522, 81300627, 81200551, 81270841, 81460148,
and 81370855), and the Prostate Cancer Foundation
Young Investigator Award 2013.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2018]版：
大类|4 区医学
小类|4 区肿瘤学4 区药学
最新[2023]版：
大类|4 区医学
小类|4 区肿瘤学4 区药学
第一作者：
第一作者机构：[a]Departments of Urology, Institute of Urology,West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China
共同第一作者：
通讯作者：
通讯机构：[a]Departments of Urology, Institute of Urology,West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China[*1]Department of Urology, Institute of Urology, West China Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, Sichuan 610041, People’s Republic of China[*2]Department of Urology, Institute of Urology, West China Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, Sichuan 610041, People’s Republic of China
推荐引用方式(GB/T 7714)：
Shi Qiu,Linghui Deng,Yige Bao,et al.Reversal of docetaxel resistance in prostate cancer by Notch signaling inhibition.[J].Anti-cancer drugs.2018,29(9):871-879.doi:10.1097/CAD.0000000000000659.
APA：
Shi Qiu,Linghui Deng,Yige Bao,Kun Jin,Xiang Tu...&Qiang Wei.(2018).Reversal of docetaxel resistance in prostate cancer by Notch signaling inhibition..Anti-cancer drugs,29,(9)
MLA：
Shi Qiu,et al."Reversal of docetaxel resistance in prostate cancer by Notch signaling inhibition.".Anti-cancer drugs 29..9(2018):871-879
