Inactivation of ID-1 Gene Induces Sensitivity of Prostate Cancer Cells to Chemotherapeutic Drugs

  • Yong-Chuan Wong
  • Xiao-Meng Zhang
  • Ming-Tak Ling
  • Xiang-Hong Wang
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 617)


Resistance to anticancer drags is one of the major reasons of treatment failure for androgen-independent prostate cancer (PC). Increase in expression of Id-1 has been reported in several types of advanced cancer including PC. It has been suggested that overexpression of Id-1 may provide an advantage for cancer cell survival and thus inactivation of Id-1 may be able to increase the susceptibility of cancer cells to apoptosis. In this study, using small RNA interfering (siRNA) technology, we inactivated the Id-1 gene in two androgen-independent PC cell lines, DU145 and PC3, and investigated whether down-regulation of Id-1 could lead to increased sensitivity of these PC cells to a commonly used anticancer drug, taxol (Tx). Our results showed that inactivation of Id-1 by sild-1 resulted in decrease in both colony forming ability and cell viability in prostate cancer cells after Tx treatment. Furthermore, the sild-1 induced sensitization to Tx was associated with activation of apoptotic pathway. In addition, c-Jun N-terminal kinase (JNK), one of the common pathways responsible for Tx-induced apoptosis, was also activated in the si-Id-1 transfected cells. Inhibition of JNK activity by a specific inhibitor, SP600125, blocked the sild-1-induced sensitivity to Tx. These results indicate that increased Id-1 expression in PC cells may play a protective role against apoptosis, and down-regulation of Id-1 may be a potential target to increase sensitivity of Tx-induced apoptosis in PC cells.


Prostate Cancer Vector Control Prostate Cancer Cell DU145 Cell Apoptotic Rate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Penson DF, Albertsen PC (2000) Lessons learnt about early prostate cancer from large scale databases: population-based pearls of wisdom. Surg Oncol 11:3–11.CrossRefGoogle Scholar
  2. 2.
    Hsing AW, Tsao L, Devesa SS (2000). International trends and patterns of prostate cancer incidence and mortality. Int J Cancer 85:60–67.PubMedCrossRefGoogle Scholar
  3. 3.
    Ling MT, Wang X, Lee DT, et al. (2004). Id-1 expression induces androgen-independent prostate cancer cell growth through activation of epidermal growth factor receptor (EGF-R). Carcinogenesis 25:517–525.PubMedCrossRefGoogle Scholar
  4. 4.
    Ouyang XS, Wang X, Ling MT, et al. (2002). Id-1 stimulates serum independent prostate cancer cell proliferation through inactivation of p16(INK4a)/pRB pathway. Carcinogenesis 23:721–725.PubMedCrossRefGoogle Scholar
  5. 5.
    Ling MT, Wang X, Ouyang XS, et al. (2002). Activation of MAPK signaling pathway is essential for Id-1 induced serum independent prostate cancer cell growth. Oncogene 21:8498–505.PubMedCrossRefGoogle Scholar
  6. 6.
    Ling MT, Wang X, Ouyang XS, et al. (2003). Id-1 expression promotes cell survival through activation of NF-kappaB signalling pathway in prostate cancer cells. Oncogene 22:4498–508.PubMedCrossRefGoogle Scholar
  7. 7.
    Ling MT, Lau TC, Zhou C, et al. (2005). Overexpression of Id-1 in prostate cancer cells promotes angiogenesis, through the activation of vascular endothelial growth factor (VEGF). Carcinogenesis 26(10):1668–1676.PubMedCrossRefGoogle Scholar
  8. 8.
    Zhang XM, Wang XH, Ling MT, et al. (2006) Inactivation of Id-1 in prostate cancer cells: A potential therapeutic target in inducing chemosensitization to taxol through activation of JNK pathway. Int J Cancer 118:2072–2081.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Yong-Chuan Wong
    • 1
  • Xiao-Meng Zhang
  • Ming-Tak Ling
  • Xiang-Hong Wang
  1. 1.Cancer Biology Lab Department of Anatomy Li Ka Shing Faculty of MedicineUniversity of Hong KongHong KongChina

Personalised recommendations