Gli2 mediates the development of castration‑resistant prostate cancer

Int J Oncol. 2020 Jul;57(1):100-112. doi: 10.3892/ijo.2020.5044. Epub 2020 Apr 13.


Glioma‑associated oncogene family zinc finger 2 (Gli2), a key component of the hedgehog signaling pathway, has been previously demonstrated to promote the malignant properties of prostate cancer in vitro. However, the role of Gli2 in the development of castration‑resistant prostate cancer (CRPC) has yet to be fully elucidated. In the present study, Gli2 expression was knocked down in androgen‑responsive prostate cancer cells using an inducible Gli2 short hairpin RNA. Suppression of Gli2 expression resulted in significant reduction of cell viability, increased the proportion of cells in the G0/G1 phases of the cell cycle and reduced the expression of genes associated with cell cycle progression. Gli2 knockdown sensitized both androgen‑dependent and ‑independent prostate cancer cells to the antiandrogen drug Casodex and prevented the outgrowth of LNCaP prostate cancer cells. In addition, Gli2 knockdown significantly suppressed the development of CRPC in a LNCaP xenograft mouse model, which was reversed by the re‑expression of Gli2. In conclusion, to the best of our knowledge, the present study was the first occasion in which the essential role of Gli2 in the development of CRPC was demonstrated, providing a potential therapeutic target for the intervention of CRPC.

Keywords: prostate cancer; castration‑resistant prostate cancer; hedgehog signaling; glioma-associated oncogene family zinc finger 2; mouse xenograft.

MeSH terms

  • Androgen Antagonists / pharmacology
  • Androgen Antagonists / therapeutic use
  • Anilides / pharmacology
  • Anilides / therapeutic use
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / genetics
  • Disease Progression
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics*
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Mice
  • Nitriles / pharmacology
  • Nitriles / therapeutic use
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Prostatic Neoplasms, Castration-Resistant / drug therapy
  • Prostatic Neoplasms, Castration-Resistant / genetics*
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • RNA, Small Interfering / metabolism
  • Tosyl Compounds / pharmacology
  • Tosyl Compounds / therapeutic use
  • Xenograft Model Antitumor Assays
  • Zinc Finger Protein Gli2 / antagonists & inhibitors
  • Zinc Finger Protein Gli2 / genetics
  • Zinc Finger Protein Gli2 / metabolism*


  • Androgen Antagonists
  • Anilides
  • Antineoplastic Agents
  • GLI2 protein, human
  • Nitriles
  • Nuclear Proteins
  • RNA, Small Interfering
  • Tosyl Compounds
  • Zinc Finger Protein Gli2
  • bicalutamide