Inhibition of PARP1 by small interfering RNA enhances docetaxel activity against human prostate cancer PC3 cells.
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.
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.
Wenqi
W
Wu
Zhenzhen
Z
Kong
Xiaolu
X
Duan
Hanliang
H
Zhu
Shujue
S
Li
Shaohua
S
Zeng
Yeping
Y
Liang
George
G
Iliakis
Zhiming
Z
Gui
Dong
D
Yang
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology; D045744:Cell Line, Tumor; D016922:Cellular Senescence; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D004815:Epidermal Growth Factor / Q000378:metabolism; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics; D011471:Prostatic Neoplasms / Q000201:enzymology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D043823:Taxoids / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001562:Benzimidazoles; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D034741:RNA, Small Interfering; D043823:Taxoids; C521013:veliparib; D000077143:Docetaxel; D004815:Epidermal Growth Factor; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt
Docetaxel; EGFR/Akt/FOXO1 signaling pathway; PARP1 siRNA; PC3 cells