DOI QR코드

DOI QR Code

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)
  • Published : 2012.06.30

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

References

  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. https://doi.org/10.1074/jbc.M106460200
  2. Artavanis-Tsakonas S, Rand MD, Lake RJ (1999). Notch signaling: cell fate control and signal integration in development. Science, 284, 770-6. https://doi.org/10.1126/science.284.5415.770
  3. Brazil DP, Hemmings BA (2001). Ten years of protein kinase B signalling: a hard Akt to follow. Trends Biochem Sci, 26, 657-64. https://doi.org/10.1016/S0968-0004(01)01958-2
  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. https://doi.org/10.1016/0092-8674(95)90039-X
  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. https://doi.org/10.1158/0008-5472.CAN-03-2505
  6. el-Deiry WS, Tokino T, Velculescu VE, et al. (1993). WAF1, a potential mediator of p53 tumor suppression. Cell, 75, 817-25. https://doi.org/10.1016/0092-8674(93)90500-P
  7. Kopan R, Ilagan MX (2009). The canonical Notch signaling pathway: unfolding the activation mechanism. Cell, 137, 216-33. https://doi.org/10.1016/j.cell.2009.03.045
  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. https://doi.org/10.1006/meth.2001.1262
  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. https://doi.org/10.1158/1078-0432.CCR-05-2570
  12. Miele L, Golde T, Osborne B (2006). Notch signaling in cancer. Curr Mol Med, 6, 905-18. https://doi.org/10.2174/156652406779010830
  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. https://doi.org/10.1158/0008-5472.CAN-05-3830
  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. https://doi.org/10.1182/blood-2007-07-102632
  15. 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. https://doi.org/10.1056/NEJMoa041318
  16. 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. https://doi.org/10.1038/nrc3035
  17. 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. https://doi.org/10.1002/pros.20824
  18. Reed SI (2002). Keeping p27(Kip1) in the cytoplasm: a second front in cancer's war on p27. Cell Cycle, 1, 389-90. https://doi.org/10.4161/cc.1.6.261
  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. https://doi.org/10.1006/jsre.1998.5483
  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. https://doi.org/10.1128/MCB.21.17.5925-5934.2001
  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. https://doi.org/10.1074/jbc.M309924200
  22. Seruga B, Ocana A, Tannock IF (2011). Drug resistance in metastatic castration-resistant prostate cancer. Nat Rev Clin Oncol, 8, 12-23. https://doi.org/10.1038/nrclinonc.2010.136
  23. Stylianou S, Clarke RB, Brennan K (2006). Aberrant activation of Notch signaling in human breast cancer. Cancer Res, 66, 1517-25. https://doi.org/10.1158/0008-5472.CAN-05-3054
  24. 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. https://doi.org/10.1056/NEJMoa040720
  25. Villaronga MA, Bevan CL, Belandia B (2008). Notch Signaling: A Potential Therapeutic Target in Prostate Cancer. Curr Cancer Drug Tar, 8, 566-80. https://doi.org/10.2174/156800908786241096
  26. 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. https://doi.org/10.1002/jcb.22770
  27. 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.
  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. https://doi.org/10.1002/ijc.22077

Cited by

  1. Hypoxia, notch signalling, and prostate cancer vol.10, pp.7, 2013, https://doi.org/10.1038/nrurol.2013.110
  2. Identification, characterization and targeting of Docetaxel-resistant prostate cancer cells vol.15, pp.1, 2013, https://doi.org/10.1038/aja.2012.133
  3. Notch1 is overexpressed in human intrahepatic cholangiocarcinoma and is associated with its proliferation, invasiveness and sensitivity to 5-fluorouracil in vitro vol.31, pp.6, 2014, https://doi.org/10.3892/or.2014.3123
  4. Notch-1 knockdown suppresses proliferation, migration and metastasis of salivary adenoid cystic carcinoma cells vol.13, pp.1, 2015, https://doi.org/10.1186/s12967-015-0520-2
  5. Prognostic Significance of Hes-1, a Downstream Target of Notch Signaling in Hepatocellular Carcinoma vol.16, pp.9, 2015, https://doi.org/10.7314/APJCP.2015.16.9.3811
  6. Metformin and Rapamycin Reduce Pancreatic Cancer Growth in Obese Prediabetic Mice by Distinct MicroRNA-Regulated Mechanisms vol.64, pp.5, 2015, https://doi.org/10.2337/db14-1132
  7. Expression and influence of Notch signaling in oral squamous cell carcinoma vol.58, pp.2, 2016, https://doi.org/10.2334/josnusd.15-0535
  8. Activation of Notch pathway is linked with epithelial-mesenchymal transition in prostate cancer cells vol.16, pp.10, 2017, https://doi.org/10.1080/15384101.2017.1312237
  9. Targeting Notch3 in Hepatocellular Carcinoma: Molecular Mechanisms and Therapeutic Perspectives vol.18, pp.1, 2016, https://doi.org/10.3390/ijms18010056
  10. Search of Neuroprotective Polyphenols Using the “Overlay” Isolation Method vol.23, pp.8, 2018, https://doi.org/10.3390/molecules23081840