Survivin Inhibition Slows Cancer Growth

Researchers using small interfering RNA molecule (siRNA) technology have demonstrated that inhibition of survivin caused up to 70% reduction in the growth of cancer cells due to a significant increase in apoptosis.

Survivin is a human gene encoding a structurally unique apoptosis inhibitor. Present during fetal development, survivin is undetectable in terminally differentiated adult tissues. However, survivin becomes prominently expressed in transformed cell lines and in all the most common human cancers of lung, colon, pancreas, prostate, and breast. Survivin is also found in high-grade non-Hodgkin's lymphomas.

Investigators at Columbus Children's Research Institute (OH, USA; www.ccri.net) prepared microarray slides comprising 63 primary rhabdomyosarcoma tumors. The slides were stained with a polyclonal antibody to survivin to identify tumors expressing this activity. Survivin-positive subcutaneous tumors were then established in mice using a rhabdomyosarcoma cell line marked with red fluorescent dye. After establishment, tumors were treated by hydrodynamic injection with a cocktail of survivin-siRNA-encoding plasmids for a period of two weeks. Tumors in control animals received injections of saline solution.

Results were published in the May 20, 2005, online edition of the Journal of Medical Genetics. Senior author Dr. Rachel Altura, assistant professor of pediatrics at Columbus Children's Research Institute, explained, "When injected directly into the tumor, or intravenously, the siRNAs interfered with survivin's function and thus, we saw a 70% reduction of the tumor growth in our study.” The survivin-siRNA-encoding plasmids had no apparent adverse effects on normal cells.

The authors believe that their findings justify further studies aimed at developing survivin inhibition into a therapeutic tool.




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