Tissue factor/FVIIa activates Bcl-2 and prevents doxorubicin-induced apoptosis in neuroblastoma cells
2008

Tissue factor and chemotherapy resistance in neuroblastoma cells

publication Evidence: moderate

Author Information

Author(s): Fang Jun, Gu Lubing, Zhu Ningxi, Tang Hao, Alvarado Carlos S, Zhou Muxiang

Primary Institution: Emory University School of Medicine

Hypothesis

The interaction between tissue factor (TF) and factor VIIa (FVIIa) regulates chemotherapy resistance in neuroblastoma cell lines.

Conclusion

The study shows that the TF/FVIIa pathway contributes to chemotherapy resistance in neuroblastoma by upregulating Bcl-2 through the JAK/STAT5 signaling pathway.

Supporting Evidence

  • TF expression was variable among neuroblastoma cell lines, with SH-EP1 cells showing high levels and SK-N-SH cells lacking TF.
  • SH-EP1 cells were more resistant to doxorubicin than SK-N-SH cells.
  • Silencing TF in SH-EP1 cells sensitized them to doxorubicin-induced apoptosis.
  • Transfection of TF into SK-N-SH cells increased resistance to doxorubicin when treated with FVIIa.
  • JAK inhibitor blocked the TF/FVIIa-induced upregulation of Bcl-2.

Takeaway

This study found that a protein called tissue factor helps cancer cells survive chemotherapy by making them resistant to a drug called doxorubicin.

Methodology

Gene and siRNA transfection were used to manipulate TF expression in neuroblastoma cell lines, followed by Western blot assays and cytotoxicity tests.

Statistical Information

P-Value

p<0.01

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1186/1471-2407-8-69

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