Short interfering RNA delivered by liposome to different human ovarian carcinoma cell lines carried in mice effectively suppressed activity of a critical intracellular enzyme and produced significant reductions in tumor weight, according to an article in the August 15 issue of Clinical Cancer Research.

The mouse model experiment, featured on the cover of the journal, demonstrated the potent delivery system for short interfering RNA to attack cancer, said senior author Anil Sood, MD, associate professor in the Departments of Gynecologic Oncology and Cancer Biology at M. D. Anderson.

"Short interfering RNA is a great technology we can use to silence genes, shutting down production of harmful proteins," Sood said. "It works well in the lab, but the question has been how to get it into tumors."

The research team used liposomes to get the silencing RNA into tumor cells, a critical step because the enzyme in question, focal adhesion kinase (FAK), is intracellular: "Targets like FAK, which are difficult to target with a drug, can be attacked with this liposomal siRNA approach, which penetrates deeply into the tumor."

Mice infected with three human ovarian cancer cell lines derived from women with advanced cancer were treated for three to five weeks with liposomes that contained either the focal adhesion kinase silencing RNA, control siRNA, or no contents. Some mice received liposomes that contained both silencing RNA and docetaxel.

Mice receiving the FAK-silencing liposome had reductions in mean tumor weight ranging from 44 to 72 percent compared with mice in control groups. Combining RNA with docetaxel boosted tumor weight reduction to the 94 to 98 percent range.
These results also held in experiments with ovarian cancer cell lines resistant to docetaxel and cisplatin.

The FAK-silencing liposome and the liposome with a chemotherapeutic agent also reduced the incidence of cancer by between 20 and 50 percent in all tested cancer lines.

In addition to its anti-tumor effect, the researchers found that the therapeutic liposome attacked the tumor's blood supply, especially when combined with chemotherapy. By inducing apoptosis among blood vessel cells, the treatment steeply reduced the number of small blood vessels feeding the tumor, cut the percentage of proliferating tumor cells and increased cancer cell death.

The next step for the FAK liposome is toxicity testing. "So far it appears to be very well-tolerated," Sood said. "We hope to develop this approach for clinical use in the future."

In addition to ovarian cancer, the same enzyme is overexpressed in colon, breast, thyroid, and head and neck cancers.