Inhibition of PARP1 by small interfering RNA enhances docetaxel activity against human prostate cancer PC3 cells

Wenqi Wu; Zhenzhen Kong; Xiaolu Duan; Hanliang Zhu; Shujue Li; Shaohua Zeng; Yeping Liang; George Iliakis; Zhiming Gui; Dong Yang

doi:10.1016/j.bbrc.2013.11.027

Inhibition of PARP1 by small interfering RNA enhances docetaxel activity against human prostate cancer PC3 cells

Biochem Biophys Res Commun. 2013 Dec 6;442(1-2):127-32. doi: 10.1016/j.bbrc.2013.11.027. Epub 2013 Nov 15.

Authors

Wenqi Wu¹, Zhenzhen Kong, Xiaolu Duan, Hanliang Zhu, Shujue Li, Shaohua Zeng, Yeping Liang, George Iliakis, Zhiming Gui, Dong Yang

Affiliation

¹ Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Guangdong Key Laboratory of Urology, China. Electronic address: wwqwml@163.com.

PMID: 24239883
DOI: 10.1016/j.bbrc.2013.11.027

Abstract

Though poly(ADP-ribose) polymerase 1 (PARP1) inhibitors have benefits in combination with radiotherapy in prostate cancers, few is known about the exactly role and underlying mechanism of PARP1 in combination with chemotherapy agents. Here our data revealed that inhibition of PARP1 by small interfering RNA (siRNA) could enhance docetaxel's activity against PC3 cells, which is associated with an accelerate repression of EGF/Akt/FOXO1 signaling pathway. Our results provide a novel role of PARP1 in transcription regulation of EGFR/Akt/FOXO1 signaling pathway and indicate that PARP1 siRNA combined with docetaxel can be an innovative treatment strategy to potentially improve outcomes in CRPC patients.

Keywords: Docetaxel; EGFR/Akt/FOXO1 signaling pathway; PARP1 siRNA; PC3 cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / pharmacology*
Benzimidazoles / pharmacology
Cell Line, Tumor
Cellular Senescence
Docetaxel
Drug Resistance, Neoplasm*
Epidermal Growth Factor / metabolism
Forkhead Box Protein O1
Forkhead Transcription Factors / metabolism
Gene Knockdown Techniques
Humans
Male
Phosphorylation / drug effects
Poly (ADP-Ribose) Polymerase-1
Poly(ADP-ribose) Polymerase Inhibitors*
Poly(ADP-ribose) Polymerases / genetics
Prostatic Neoplasms / enzymology*
Proto-Oncogene Proteins c-akt / metabolism
RNA, Small Interfering / genetics
Signal Transduction
Taxoids / pharmacology*

Substances

Antineoplastic Agents
Benzimidazoles
FOXO1 protein, human
Forkhead Box Protein O1
Forkhead Transcription Factors
Poly(ADP-ribose) Polymerase Inhibitors
RNA, Small Interfering
Taxoids
veliparib
Docetaxel
Epidermal Growth Factor
PARP1 protein, human
Poly (ADP-Ribose) Polymerase-1
Poly(ADP-ribose) Polymerases
Proto-Oncogene Proteins c-akt