PMID- 32586404
OWN - NLM
STAT- MEDLINE
DCOM- 20210618
LR  - 20210618
IS  - 1757-6512 (Electronic)
IS  - 1757-6512 (Linking)
VI  - 11
IP  - 1
DP  - 2020 Jun 26
TI  - Inhibition of Notch pathway enhances the anti-tumor effect of docetaxel in 
      prostate cancer stem-like cells.
PG  - 258
LID - 10.1186/s13287-020-01773-w [doi]
LID - 258
AB  - BACKGROUND: Prostate cancer stem-like cells (PCSCs) likely participate in tumor 
      progression and recurrence and demonstrate resistance to chemotherapy. The Notch 
      pathway plays a role in the maintenance of the stemness in PCSCs. This study 
      aimed to investigate the efficacy of Notch signaling inhibition as an adjuvant to 
      docetaxel (DOX) in PCSCs. METHODS: PCSCs derived from the PC-3 cell line were 
      examined for Notch-1 expression. The effect of Notch inhibition on response to 
      DOX was evaluated in PCSCs in vitro and in murine models using a gamma-secretase 
      inhibitor (GSI), PF-03084014. Impacts on cell proliferation, apoptosis, cell 
      cycle, and sphere formation were evaluated. RESULTS: PC-3 PCSCs expressed 
      elevated Notch-1 mRNA compared with PC-3 parental cells. The combination of GSI 
      with DOX promoted DOX-induced cell growth inhibition, apoptosis, cell cycle 
      arrest, and sphere formation in PCSCs. In nude mice bearing PC-3 PCSC-derived 
      tumors, the combination of GSI and DOX reduced the tumor growth, which was 
      associated with the decreased Notch-1 expression in tumor tissues. CONCLUSIONS: 
      These results reveal that inhibition of the Notch pathway enhances the anti-tumor 
      effect of DOX in PC-3 PCSCs, and suggest that Notch inhibition may have clinical 
      benefits in targeting PCSCs.
FAU - Wang, Lei
AU  - Wang L
AD  - Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan 
      University, Wuhan, 430071, China.
AD  - Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, 430071, China.
AD  - Hubei Cancer Clinical Study Center, Wuhan, 430071, China.
FAU - Zi, Hao
AU  - Zi H
AD  - Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan 
      University, Wuhan, 430071, China.
FAU - Luo, Yi
AU  - Luo Y
AD  - Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, 
      China.
FAU - Liu, Tongzu
AU  - Liu T
AD  - Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, 
      China.
FAU - Zheng, Hang
AU  - Zheng H
AD  - Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, 
      China.
FAU - Xie, Conghua
AU  - Xie C
AD  - Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan 
      University, Wuhan, 430071, China.
AD  - Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, 430071, China.
AD  - Hubei Cancer Clinical Study Center, Wuhan, 430071, China.
FAU - Wang, Xinghuan
AU  - Wang X
AD  - Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan 
      University, Wuhan, 430071, China.
AD  - Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, 
      China.
FAU - Huang, Xing
AU  - Huang X
AD  - Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan 
      University, Wuhan, 430071, China. hxsurgeon@whu.edu.cn.
AD  - Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, 
      China. hxsurgeon@whu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200626
PL  - England
TA  - Stem Cell Res Ther
JT  - Stem cell research & therapy
JID - 101527581
RN  - 0 (Receptors, Notch)
RN  - 15H5577CQD (Docetaxel)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Docetaxel/pharmacology
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Nude
MH  - Neoplastic Stem Cells
MH  - *Prostatic Neoplasms/drug therapy/genetics
MH  - Receptors, Notch/genetics
PMC - PMC7318403
OTO - NOTNLM
OT  - Cancer stem cells
OT  - Docetaxel resistance
OT  - Notch
OT  - Prostate cancer
OT  - gamma-Secretase inhibitor
COIS- The authors declare that they have no competing interests.
EDAT- 2020/06/27 06:00
MHDA- 2021/06/22 06:00
PMCR- 2020/06/26
CRDT- 2020/06/27 06:00
PHST- 2020/03/08 00:00 [received]
PHST- 2020/06/16 00:00 [accepted]
PHST- 2020/05/22 00:00 [revised]
PHST- 2020/06/27 06:00 [entrez]
PHST- 2020/06/27 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/06/26 00:00 [pmc-release]
AID - 10.1186/s13287-020-01773-w [pii]
AID - 1773 [pii]
AID - 10.1186/s13287-020-01773-w [doi]
PST - epublish
SO  - Stem Cell Res Ther. 2020 Jun 26;11(1):258. doi: 10.1186/s13287-020-01773-w.