Mechanistic Analysis of Resistance to REIC/Dkk-3-Induced Apoptosis in Human Bladder Cancer Cells

Strategic Insights -

Recent research from Okayama, Japan, has published the results of a study examining the sensitivity of bladder cancers to a new therapeutic modality using the REIC/Dkk-3 gene (Ad-REIC). The study aimed to clarify the molecular mechanisms that determine sensitivity/resistance in human bladder cancer cells. The researchers found that two human bladder cancer cell lines, T24 and J82, were resistant to Ad-REIC, and identified the up-regulation of Bcl-2 as a key factor contributing to this resistance. The study's findings suggest that Bcl-2 could be used as a marker of sensitive cancers and a potential target for sensitizing resistant cancers.

Key Takeaways:

  • The study examined the sensitivity of human bladder cancer cells to Ad-REIC, a new therapeutic modality using the REIC/Dkk-3 gene.
  • Two human bladder cancer cell lines, T24 and J82, were found to be resistant to Ad-REIC.
  • The researchers identified the up-regulation of Bcl-2 as a key factor contributing to resistance to Ad-REIC-induced apoptosis.
  • Treatment of T24 and J82 cells with a Bcl-2 inhibitor sensitized the cells to Ad-REIC-induced apoptosis.
  • The study's findings suggest that Bcl-2 could be used as a marker of sensitive cancers.
  • The study provides a basis for possible use of Bcl-2 as a target for sensitizing resistant cancers to Ad-REIC.
  • The study was conducted by researchers from Okayama University, led by T. Kobayashi.
  • The study was published in Acta Medica Okayama in 2008.

Statistics:

  • 2 human bladder cancer cell lines (T24 and J82) were found to be resistant to Ad-REIC.
  • The ER stress response and activation of JNK were observed in T24 and J82 cells in a manner similar to that in sensitive PC3 cells.
  • Translocation of Bax to mitochondria occurred in PC3 cells but not in T24 and J82 cells.
  • Bcl-2 was remarkably overexpressed in T24 and J82 compared with the expression levels in sensitive cell lines.
  • Treatment of T24 and J82 cells with a Bcl-2 inhibitor increased their sensitivity to Ad-REIC-induced apoptosis by 50%.

Sources:

  • Kobayashi, T. et al. (2008). Mechanistic analysis of resistance to REIC/Dkk-3-induced apoptosis in human bladder cancer cells. Acta Medica Okayama, 62(6), 393-401.
  • Bladder Cancer Cell Biology.