Browse > Article
http://dx.doi.org/10.7314/APJCP.2012.13.6.2485

siRNA-mediated Silencing of Notch-1 Enhances Docetaxel Induced Mitotic Arrest and Apoptosis in PCa Cells  

Ye, Qi-Fa (Engineering and Technology Research Center for Transplantation Medicine of the National Ministry of Health)
Zhang, Yi-Chuan (Engineering and Technology Research Center for Transplantation Medicine of the National Ministry of Health)
Peng, Xiao-Qing (Department of Gastroenterology, The Third Xiangya Hospital, Central South University)
Long, Zhi (Department of Urology, The Third Xiangya Hospital, Central South University)
Ming, Ying-Zi (Engineering and Technology Research Center for Transplantation Medicine of the National Ministry of Health)
He, Le-Ye (Department of Urology, The Third Xiangya Hospital, Central South University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.13, no.6, 2012 , pp. 2485-2489 More about this Journal
Abstract
Purpose: Notch is an important signaling pathway that regulates cell fate, stem cell maintenance and the initiation of differentiation in many tissues. It has been reported that activation of Notch-1 contributes to tumorigenesis. However, whether Notch signaling might have a role in chemoresistance of prostate cancer is unclear. This study aimed to investigate the effects of Notch-1 silencing on the sensitivity of prostate cancer cells to docetaxel treatment. Methods: siRNA against Notch-1 was transfected into PC-3 prostate cancer cells. Proliferation, apoptosis and cell cycle distribution were examined in the presence or absence of docetaxel by MTT and flow cytometry. Expression of $p21^{waf1/cip1}$ and Akt as well as activation of Akt in PC-3 cells were detected by Western blot and Real-time PCR. Results: Silencing of Notch-1 promoted docetaxel induced cell growth inhibition, apoptosis and cell cycle arrest in PC-3 cells. In addition, these effects were associated with increased $p21^{waf1/cip1}$ expression and decreased Akt expression and activation in PC-3 cells. Conclusion: Notch-1 promotes chemoresistance of prostate cancer and could be a potential therapeutic target.
Keywords
Notch signaling; prostate cancer; siRNA; cell cycle; apoptosis; $p21^{waf1/cip1}$; Akt;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Ando T, Kawabe T, Ohara H, et al (2001). Involvement of the interaction between p21 and proliferating cell nuclear antigen for the maintenance of G2/M arrest after DNA damage. J Biol Chem, 276, 42971-7.   DOI   ScienceOn
2 Artavanis-Tsakonas S, Rand MD, Lake RJ (1999). Notch signaling: cell fate control and signal integration in development. Science, 284, 770-6.   DOI   ScienceOn
3 Brazil DP, Hemmings BA (2001). Ten years of protein kinase B signalling: a hard Akt to follow. Trends Biochem Sci, 26, 657-64.   DOI   ScienceOn
4 Deng C, Zhang P, Harper JW, et al (1995). Mice lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control. Cell, 82, 675-84.   DOI   ScienceOn
5 De Siervi A, Marinissen M, Diggs J, et al. (2004). Transcriptional activation of $p21^{(waf1/cip1)}$ by alkylphospholipids: role of the mitogen-activated protein kinase pathway in the transactivation of the human $p21^{(waf1/cip1)}$ promoter by Sp1. Cancer Res, 64, 743-50.   DOI
6 el-Deiry WS, Tokino T, Velculescu VE, et al. (1993). WAF1, a potential mediator of p53 tumor suppression. Cell, 75, 817-25.   DOI   ScienceOn
7 Kopan R, Ilagan MX (2009). The canonical Notch signaling pathway: unfolding the activation mechanism. Cell, 137, 216-33.   DOI
8 Livak KJ, Schmittgen TD (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 25, 402-8.   DOI   ScienceOn
9 Li Z, Wang J, Gong L, et al (2011). Correlation of Delta-like ligand 4 (DLL4) with VEGF and HIF-1alpha expression in human glioma. Asian Pac J Cancer Prev, 12, 215-8.
10 McGrogan BT, Gilmartin B, Camey DN, McCann A (2008). Taxanes, microtubules and chemoresistant breast cancer. Bba Rev Cancer, 1785, 96-132.
11 Miele L (2006). Notch signaling. Clin Cancer Res, 12, 1074-79.   DOI
12 Miele L, Golde T, Osborne B (2006). Notch signaling in cancer. Curr Mol Med, 6, 905-18.   DOI   ScienceOn
13 Mungamuri SK, Yang YH, Thor AD, Somasundaram K (2006). Survival signaling by Notch1: Mammalian target of rapamycin (mTOR)-dependent inhibition of p53. Cancer Res, 66, 4715-24.   DOI
14 Nefedova Y, Sullivan DM, Bolick SC, et al (2008). Inhibition of Notch signaling induces apoptosis of myeloma cells and enhances sensitivity to chemotherapy. Blood, 111, 2220-29.   DOI
15 Reed SI (2002). Keeping p27(Kip1) in the cytoplasm: a second front in cancer's war on p27. Cell Cycle, 1, 389-90.   DOI
16 Petrylak DP, Tangen CM, Hussain MHA, et al (2004). Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. New Engl J Med, 351, 1513-20.   DOI
17 Ranganathan P, Weaver KL, Capobianco AJ (2011). Notch signalling in solid tumours: a little bit of everything but not all the time. Nat Rev Cancer, 11, 338-51.   DOI
18 Reagan-Shaw S, Nihal M, Ahsan H, et al (2008). Combination of vitamin E and selenium causes an induction of apoptosis of human prostate cancer cells by enhancing Bax/Bcl-2 ratio. Prostate, 68, 1624-34.   DOI   ScienceOn
19 Rigberg DA, Blinman TA, Kim FS, et al (1999). Antisense blockade of p21/WAF1 decreases radiation-induced G2 arrest in esophageal squamous cell carcinoma. J Surg Res, 81, 6-10.   DOI
20 Ronchini C, Capobianco AJ (2001). Induction of cyclin D1 transcription and CDK2 activity by Notch(ic): Implication for cell cycle disruption in transformation by Notch(ic). Mol Cell Biol, 21, 5925-34.   DOI
21 Sade H, Krishna S, Sarin A (2004). The anti-apoptotic effect of Notch-1 requires p56lck-dependent, Akt/PKB-mediated signaling in T cells. J Biol Chem, 279, 2937-44.   DOI
22 Seruga B, Ocana A, Tannock IF (2011). Drug resistance in metastatic castration-resistant prostate cancer. Nat Rev Clin Oncol, 8, 12-23.   DOI
23 Stylianou S, Clarke RB, Brennan K (2006). Aberrant activation of Notch signaling in human breast cancer. Cancer Res, 66, 1517-25.   DOI
24 Zhang F, Chen A, Chen J, et al (2011). SiRNA-mediated silencing of beta-catenin suppresses invasion and chemosensitivity to doxorubicin in MG-63 osteosarcoma cells. Asian Pac J Cancer Prev, 12, 239-45.
25 Tannock IF, de Wit R, Berry WR, et al (2004). Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. New Engl J Med, 351, 1502-12.   DOI
26 Villaronga MA, Bevan CL, Belandia B (2008). Notch Signaling: A Potential Therapeutic Target in Prostate Cancer. Curr Cancer Drug Tar, 8, 566-80.   DOI
27 Wang ZW, Li YW, Ahmad A, et al (2011). Down-Regulation of Notch-1 Is Associated With Akt and FoxM1 in Inducing Cell Growth Inhibition and Apoptosis in Prostate Cancer Cells. J Cell Biochem, 112, 78-88.   DOI
28 Zhang YX, Wang ZW, Ahmed F, et al (2006). Down-regulation of Jagged-1 induces cell growth inhibition and S phase arrest in prostate cancer cells. Int J Cancer, 119, 2071-7.   DOI