Researchers found that Interleukin-8 (IL-8) production, which they associated with a lower median survival in ovarian cancer patients, can be stifled by a particular siRNA wrapped in a fatty nanoparticle.
To examine IL-8's role in ovarian cancer, the researchers analyzed tumors from 102 patients diagnosed and treated between 1988 and 2006. Of those, 43 had tumors with high levels of IL-8 and 59 had low levels. The median survival of those with high IL-8 tumors was 1.62 years compared with 3.79 years for those with low expression.
All 43 tumors with high expression of IL-8 were high grade, and 42 of 43 were advanced, either stage III or IV tumors. By comparison, 10 of 59 tumors with low IL-8 expression were early stage, and six were of low grade.
The team also confirmed in a lab experiment that a specific siRNA silences IL-8. They then tested it against two lines of ovarian cancer in a mouse model. They packaged siRNA that stymies IL-8 into a small ball of liposome, a combination they developed to deliver siRNA to tumors.
Injections of the IL-8 siRNA liposome shrank tumors in mice receiving the injection. Mice receiving the IL-8 siRNA plus taxane-based chemotherapy docetaxel had greater tumor reduction compared to just docetaxel.
They also tested the approach in mice with an ovarian cancer cell line known to be resistant to taxane-based drugs. IL-8 siRNA alone reduced the size of these tumors by 47%, according to the research team. In combination with docetaxel it reduced tumor size by 77%, they add. The researchers hypothesize that the combination resensitizes a resistant tumor to taxanes.
The study was conducted by investigators at the University of Texas M. D. Anderson Cancer Center, Nebraska Medical Center, and the University of Iowa. The paper is published in the Journal of the National Cancer Institute.